Anti-Cancer Drugs最新文献_第10页

KAT8 enhances the resistance of lung cancer cells to cisplatin by acetylation of PKM2. KAT8 通过对 PKM2 进行乙酰化增强了肺癌细胞对顺铂的耐药性。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-09-01 Epub Date: 2024-05-20 DOI: 10.1097/CAD.0000000000001622

Zhenyu Li, Xiangji Lu, Jing Zhang, Tao Liu, Mingzhi Xu, Shuai Liu, Junguo Liang

{"title":"KAT8 enhances the resistance of lung cancer cells to cisplatin by acetylation of PKM2.","authors":"Zhenyu Li, Xiangji Lu, Jing Zhang, Tao Liu, Mingzhi Xu, Shuai Liu, Junguo Liang","doi":"10.1097/CAD.0000000000001622","DOIUrl":"10.1097/CAD.0000000000001622","url":null,"abstract":"Cisplatin (CDDP)-based chemotherapy resistance is a major challenge for lung cancer treatment. PKM2 is the rate-limiting enzyme of glycolysis, which is associated with CDDP resistance. KAT8 is an acetyltransferase that regulates lung cancer progression. Thus, we aimed to explore whether KAT8 regulates PKM2 acetylation to participate in CDDP resistance. CDDP resistance was analyzed by CCK-8, flow cytometry and western blotting. To explore the regulation of KAT8 on PKM2, coimmunoprecipitation (Co-IP), immunofluorescence and immunoprecipitation followed by western blotting were performed. Glycolysis was determined using glucose consumption, lactate production, ATP level detection kits and extracellular acidification rate assay. We observed that KAT8 levels were downregulated in CDDP-treated A549 and PC9 cells. Interference with KAT8 inhibited cell viability, promoted apoptosis and upregulated PARP1 and cleaved-PARP1 levels of A549 cells treated with CDDP, suggesting the sensitivity to CDDP was enhanced, while KAT8 overexpression attenuated the CDDP sensitivity. Moreover, KAT8 interacted with PKM2 to promote the PKM2 K433 acetylation. PKM2 K433 mutated plasmids inhibited the si-KAT8-regulated cell viability, apoptosis and glycolysis compared with PKM2-WT. Besides, KAT8 reversed the inhibition of tumor growth caused by CDDP. In conclusion, KAT8-mediated PKM2 K433 acetylation was associated with the resistance of lung cancer cells to CDDP. The findings may provide a new idea for the treatment of CDDP-resistant lung cancer.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"732-740"},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141074643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhancing the management of locally advanced head and neck malignancies and cases with local/neck recurrence and metastasis through the integration of anlotinib with concurrent radiochemotherapy. 通过将安洛替尼与同期放化疗相结合，加强对局部晚期头颈部恶性肿瘤以及局部/颈部复发和转移病例的治疗。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-09-01 Epub Date: 2024-05-27 DOI: 10.1097/CAD.0000000000001621

Xiaojing Tie, Hang Li, Ling Gao, Peijie Liu, Yaohong Gao, Mingxin Jin, Guangting Duan, Zhenying Yi

{"title":"Enhancing the management of locally advanced head and neck malignancies and cases with local/neck recurrence and metastasis through the integration of anlotinib with concurrent radiochemotherapy.","authors":"Xiaojing Tie, Hang Li, Ling Gao, Peijie Liu, Yaohong Gao, Mingxin Jin, Guangting Duan, Zhenying Yi","doi":"10.1097/CAD.0000000000001621","DOIUrl":"10.1097/CAD.0000000000001621","url":null,"abstract":"The aim of this study is to assess the effectiveness and safety of anlotinib in conjunction with concurrent radiochemotherapy for the treatment of locally advanced head and neck malignant tumors, including cases exhibiting local or neck recurrence and metastasis. Between June 2020 and June 2023, 42 patients diagnosed with locally advanced head and neck malignant tumors or presenting with local or neck recurrence and metastasis were recruited. These individuals received treatment that combined anlotinib with concurrent radiochemotherapy, followed by a minimum of two cycles of oral anlotinib upon completion of the initial treatment regimen. Among the 19 patients diagnosed with nasopharyngeal carcinoma, 14 patients attained a complete response, while four patients achieved partial response, resulting in an overall response rate of 94.74% (18/19). Conversely, among the 23 patients with non-nasopharyngeal carcinoma, two patients achieved complete response and 16 attained partial response, yielding a response rate of 78.26% (18/23). The 6-month progression-free survival rate was 95.24%. After treatment, serum vascular endothelial growth factor receptor levels exhibited a significant decrease compared with pretreatment levels. Notably, no instances of treatment-related serious adverse reactions were recorded. The combination of anlotinib with concurrent radiochemotherapy demonstrates favorable efficacy in managing locally advanced head and neck malignant tumors, including instances of local or neck recurrence and metastasis. Furthermore, the treatment regimen is characterized by an acceptable safety profile and tolerability.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"774-779"},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptome and metabolome sequencing identifies glutamate and LPAR1 as potential factors of anlotinib resistance in thyroid cancer. 转录组和代谢组测序发现谷氨酸和LPAR1是甲状腺癌患者对安罗替尼耐药的潜在因素。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-09-01 Epub Date: 2024-05-31 DOI: 10.1097/CAD.0000000000001626

Bin Liu, Ying Peng, Yanjun Su, Chang Diao, Jun Qian, Xiangxiang Zhan, Ruochuan Cheng

{"title":"Transcriptome and metabolome sequencing identifies glutamate and LPAR1 as potential factors of anlotinib resistance in thyroid cancer.","authors":"Bin Liu, Ying Peng, Yanjun Su, Chang Diao, Jun Qian, Xiangxiang Zhan, Ruochuan Cheng","doi":"10.1097/CAD.0000000000001626","DOIUrl":"10.1097/CAD.0000000000001626","url":null,"abstract":"Objective: To explore the mechanism of anlotinib resistance in thyroid carcinoma.Methods: We constructed an anlotinib-resistant thyroid carcinoma cell line and observed the effect of drug resistance on the functional activity of these cell lines. Transcriptome sequencing and metabolomic sequencing combined with biosynthesis analysis were used to explore and screen possible drug resistance regulatory pathways.Results: Through transcriptomic sequencing analysis of drug-resistant cell lines, it was found that the differentially expressed genes of drug-resistant strains were enriched mainly in the interleukin 17, transforming growth factor-β, calcium, peroxisome proliferator activated receptor, and other key signaling pathways. A total of 354 differentially expressed metabolic ions were screened using liquid chromatography-mass spectrometry/mass spectrometry to determine the number of metabolic ions in the drug-resistant strains. The results of the Venn diagram correlation analysis showed that glutamate is closely related to multiple pathways and may be an important regulatory factor of anlotinib resistance in thyroid carcinoma. In addition, eight common differentially expressed genes were screened by comparing the gene expression profiling interactive analysis database and sequencing results. Further quantitative real time polymerase chain reaction verification, combined with reports in the literature, showed that LPAR1 may be an important potential target.Conclusion: This is the first study in which the drug resistance of thyroid cancer to anlotinib was preliminarily discussed. We confirmed that anlotinib resistance in thyroid cancer promotes the progression of malignant biological behavior. We conclude that glutamate may be a potential factor for anlotinib resistance in thyroid cancer and that LPAR1 is also a potentially important target.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"741-751"},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

First case report of sunvozertinib for the treatment of HER2 exon 20 insertion in lung adenocarcinoma. 舒伐他尼治疗肺腺癌 HER2 20 外显子插入的首个病例报告。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-09-01 Epub Date: 2024-06-26 DOI: 10.1097/CAD.0000000000001628

Tao Luan, Xinqing Lin, Xiaohong Xie, Gang Yang, Shuaiying Wang, Jianqing Hao, Chengzhi Zhou

{"title":"First case report of sunvozertinib for the treatment of HER2 exon 20 insertion in lung adenocarcinoma.","authors":"Tao Luan, Xinqing Lin, Xiaohong Xie, Gang Yang, Shuaiying Wang, Jianqing Hao, Chengzhi Zhou","doi":"10.1097/CAD.0000000000001628","DOIUrl":"10.1097/CAD.0000000000001628","url":null,"abstract":"Human epidermal growth factor receptor 2 (HER2) is a transmembrane glycoprotein receptor with intracellular tyrosine kinase activity. It is generally considered as a poor prognostic marker. Targeted therapies, such as small molecule tyrosine kinase inhibitors (TKIs), showed limited efficacy in HER2-mutant advanced nonsmall cell lung cancer (NSCLC). In the 2023 National Comprehensive Cancer Network guidelines for NSCLC, antibody-drug conjugate trastuzumab emtansine is recommended for the treatment of HER2-mutant lung cancer. However, this medication is currently not approved in certain regions. So it is necessary to explore alternative treatment options for HER2-mutant NSCLC patients. In our study of a patient with HER2 exon 20 insertion lung adenocarcinoma who had previously failed multiple epidermal growth factor receptor (EGFR)-TKI treatments, we discovered that sunvozertinib could stabilize the patient's condition, achieving a progression-free survival of 87 days. This is a novel finding that may provide new treatment options for HER2 exon 20 insertion patients who have failed TKI therapy.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"757-760"},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Study on the therapeutic effect of sintilimab combined with modified DCF regimen on advanced gastric cancer and its impact on Th1/Th2 immune balance. 研究辛替利马联合改良 DCF 方案对晚期胃癌的疗效及其对 Th1/Th2 免疫平衡的影响。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-09-01 Epub Date: 2024-06-28 DOI: 10.1097/CAD.0000000000001629

Lili Cai, Lan Qu, Yanjie Cheng, Jinfeng Zhang, Shiying Li, Shenghong Wu

{"title":"Study on the therapeutic effect of sintilimab combined with modified DCF regimen on advanced gastric cancer and its impact on Th1/Th2 immune balance.","authors":"Lili Cai, Lan Qu, Yanjie Cheng, Jinfeng Zhang, Shiying Li, Shenghong Wu","doi":"10.1097/CAD.0000000000001629","DOIUrl":"10.1097/CAD.0000000000001629","url":null,"abstract":"The aim of this study was to observe the therapeutic effect of sintilimab combined with a modified docetaxel + cisplatin + fluorouracil (DCF) regimen on advanced gastric cancer and its effect on Th1/Th2 immune balance. Ninety-eight cases of advanced gastric cancer patients who visited our hospital from April 2020 to May 2022 were selected and divided into 48 cases each in the conventional group and the research group by random number table method; the DCF regimen was adopted in the conventional group, and sintilimab combined with modified DCF regimen was adopted in the research group, and the therapeutic effects of the patients in the two groups and the changes of Th1/Th2 immune indexes were compared. CEA, CA199, CA242, CD168 AQ3, and IL-4 in the study group were lower than those in the conventional group at the end of three cycles of treatment, and the difference was statistically significant ( P < 0.001). The levels of IFN-γ and IL-4 in the study group at the end of three cycles of treatment were higher than those in the conventional group ( P < 0.001). The incidence of adverse reactions during treatment in the study group was lower than that in the conventional group ( P < 0.001), and the grading of adverse reactions in the study group was milder than that in the conventional group. Sintilimab combined with a modified DCF regimen in the treatment of advanced gastric cancer not only improves the therapeutic effect but also positively affects the Th1/Th2 immune balance, which provides better immune regulation for patients with advanced gastric cancer.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"780-788"},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Combating anoikis resistance: bioactive compounds transforming prostate cancer therapy. 对抗抗药性：生物活性化合物改变前列腺癌疗法。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-09-01 Epub Date: 2024-05-14 DOI: 10.1097/CAD.0000000000001616

Shweta Gulia, Prakash Chandra, Asmita Das

{"title":"Combating anoikis resistance: bioactive compounds transforming prostate cancer therapy.","authors":"Shweta Gulia, Prakash Chandra, Asmita Das","doi":"10.1097/CAD.0000000000001616","DOIUrl":"10.1097/CAD.0000000000001616","url":null,"abstract":"The study aims to discuss the challenges associated with treating prostate cancer (PCa), which is known for its complexity and drug resistance. It attempts to find differentially expressed genes (DEGs), such as those linked to anoikis resistance and circulating tumor cells, in PCa samples. This study involves analyzing the functional roles of these DEGs using gene enrichment analysis, and then screening of 102 bioactive compounds to identify a combination that can control the expression of the identified DEGs. In this study, 53 DEGs were identified from PCa samples including anoikis-resistant PCa cells and circulating tumor cells in PCa. Gene enrichment analysis with regards to functional enrichment of DEGs was performed. An inclusive screening process was carried out among 102 bioactive compounds to identify a combination capable of affecting and regulating the expression of selected DEGs. Eventually, gastrodin, nitidine chloride, chenodeoxycholic acid, and bilobalide were selected, as their combination demonstrated ability to modulate expression of 50 out of the 53 genes targeted. The subsequent analysis focused on investigating the biological pathways and processes influenced by this combination. The findings revealed a multifaceted and multidimensional approach to tumor regression. The combination of bioactive compounds exhibited effects on various genes including those related to production of inflammatory cytokines, cell proliferation, autophagy, apoptosis, angiogenesis, and metastasis. The current study has made a valuable contribution to the development of a combination of bioactive natural compounds that can significantly impede the development of treatment resistance in prostate tumor while countering the tumors' evasion of the immune system. The implications of this study are highly significant as it suggests the creation of an enhanced immunotherapeutic, natural therapeutic concoction with combinatorial potential.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"687-697"},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HER2 exon 20 mutant non-small cell lung cancer with complete remission of intracranial metastases with trastuzumab deruxtecan: a case report. HER2 20 号外显子突变的非小细胞肺癌，曲妥珠单抗德鲁司坦治疗后颅内转移完全缓解：病例报告。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-09-01 Epub Date: 2024-05-16 DOI: 10.1097/CAD.0000000000001625

Ali Kaan Güren, Erkam Kocaaslan, Yeşim Ağyol, Nargiz Majidova, Nadiye Sever, Pinar Erel, Abdussamet Çelebi, Rukiye Arikan, Selver Işik, Murat Sari, İbrahim Vedat Bayoğlu, Osman Köstek

{"title":"HER2 exon 20 mutant non-small cell lung cancer with complete remission of intracranial metastases with trastuzumab deruxtecan: a case report.","authors":"Ali Kaan Güren, Erkam Kocaaslan, Yeşim Ağyol, Nargiz Majidova, Nadiye Sever, Pinar Erel, Abdussamet Çelebi, Rukiye Arikan, Selver Işik, Murat Sari, İbrahim Vedat Bayoğlu, Osman Köstek","doi":"10.1097/CAD.0000000000001625","DOIUrl":"10.1097/CAD.0000000000001625","url":null,"abstract":"Trastuzumab deruxtecan (T-DXd) is a novel anti-HER2 antibody-drug conjugate formed by the combination of trastuzumab and deruxtecan. It is used in human epidermal growth factor 2 receptor (HER2) mutant breast, stomach and colorectal cancers as well as non-small cell lung cancer (NSCLC). The 58-year-old denovo metastatic NSCLC patient we will discuss here progressed with newly developing brain metastasis under first-line carboplatin/paclitaxel treatment. After next generation sequencing revealed a mutation in the ERBB2 gene located in exon 20, we administered T-DXd to our patient. While a significant improvement was observed in the clinical condition of the patient after one course of treatment, brain metastases were found to be in complete response in control screening after four courses of treatment. Systemic screening with PET/computed tomography showed nearly complete regression of the primary lesion, metastatic lymphadenopathies, and surrenal metastases. T-DXd may be successfully used in HER2 mutant metastatic NSCLC patients. In addition, it can also be successfully used in patients with central nervous system metastases with or without cranial radiotherapy.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":"35 8","pages":"769-773"},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Screening of a kinase inhibitor library identified novel targetable kinase pathways in triple-negative breast cancer. 对激酶抑制剂库进行筛选，发现了三阴性乳腺癌中新的可靶向激酶通路。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-08-21 DOI: 10.1097/CAD.0000000000001658

Caroline H Rinderle, Christopher V Baker, Courtney B Lagarde, Khoa Nguyen, Sara Al-Ghadban, Margarite D Matossian, Van T Hoang, Elizabeth C Martin, Bridgette M Collins-Burow, Simak Ali, David H Drewry, Matthew E Burow, Bruce A Bunnell

{"title":"Screening of a kinase inhibitor library identified novel targetable kinase pathways in triple-negative breast cancer.","authors":"Caroline H Rinderle, Christopher V Baker, Courtney B Lagarde, Khoa Nguyen, Sara Al-Ghadban, Margarite D Matossian, Van T Hoang, Elizabeth C Martin, Bridgette M Collins-Burow, Simak Ali, David H Drewry, Matthew E Burow, Bruce A Bunnell","doi":"10.1097/CAD.0000000000001658","DOIUrl":"10.1097/CAD.0000000000001658","url":null,"abstract":"Triple-negative breast cancer (TNBC) is a highly invasive breast cancer subtype that is challenging to treat due to inherent heterogeneity and absence of estrogen, progesterone, and human epidermal growth factor 2 receptors. Kinase signaling networks drive cancer growth and development, and kinase inhibitors are promising anti-cancer strategies in diverse cancer subtypes. Kinase inhibitor screens are an efficient, valuable means of identifying compounds that suppress cancer cell growth in vitro, facilitating the identification of kinase vulnerabilities to target therapeutically. The Kinase Chemogenomic Set is a well-annotated library of 187 kinase inhibitor compounds that indexes 215 kinases of the 518 in the known human kinome representing various kinase networks and signaling pathways, several of which are understudied. Our screen revealed 14 kinase inhibitor compounds effectively inhibited TNBC cell growth and proliferation. Upon further testing, three compounds, THZ531, THZ1, and PFE-PKIS 29, had the most significant and consistent effects across a range of TNBC cell lines. These cyclin-dependent kinase (CDK)12/CDK13, CDK7, and phosphoinositide 3-kinase inhibitors, respectively, decreased metabolic activity in TNBC cell lines and promote a gene expression profile consistent with the reversal of the epithelial-to-mesenchymal transition, indicating these kinase networks potentially mediate metastatic behavior. These data identified novel kinase targets and kinase signaling pathways that drive metastasis in TNBC.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibiting FGFR by toadflax reverses erlotinib resistance in nonsmall cell lung cancer. 蟾蜍麻抑制FGFR可逆转非小细胞肺癌的厄洛替尼耐药。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-08-13 DOI: 10.1097/CAD.0000000000001649

Bateer Han, Ying Ma, Shuguang Bao, Hui Gao, Yanqing Gao, Qiang Guo, Ao Li, Meitao Li, Rong Yu, Hongwei Wang

{"title":"Inhibiting FGFR by toadflax reverses erlotinib resistance in nonsmall cell lung cancer.","authors":"Bateer Han, Ying Ma, Shuguang Bao, Hui Gao, Yanqing Gao, Qiang Guo, Ao Li, Meitao Li, Rong Yu, Hongwei Wang","doi":"10.1097/CAD.0000000000001649","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001649","url":null,"abstract":"This study aims to demonstrate the effect of toadflax (bufalin) on erlotinib resistance in nonsmall cell lung cancer (NSCLC) by inhibiting the fibroblast growth factor receptor (FGFR). The microfluidic mobility transferase and caliper mobility-shift assays were employed to detect the FGFR inhibition by bufalin and the binding reversibility. Further, the inhibitory effects of bufalin were determined in HCC827 and HCC827/ER cells in vitro, investigating relative FGFR overexpression by quantitative reverse transcriptase-PCR (RT-qPCR) and FGFR downstream proteins, that is, FGFR substrate 2 (FRS2), extracellular signal-regulated kinase (ERK), and S6 by western blot analysis. Finally, HCC827/ER-inoculated xenograft tumors were constructed to observe the effects of bufalin and bufalin + erlotinib intervention on tumor growth. Bufalin inhibited FGFR by reversibly binding to FGFR1. In addition, the western blot analysis indicated a significant reduction in the expression levels of FGFR, FRS2, ERK, and S6 proteins in HCC827 and HCC827/ER cells, increasing the expression levels of apoptotic caspase-3 and poly-(ADP-ribose) polymerase proteins. Bufalin + erlotinib combination significantly inhibited the apoptosis of HCC827/ER cells and subsequent tumor growth in vivo. In addition, FGFR overexpression significantly reversed the sensitivity of bufalin to HCC827/ER cells, promoting the value-addition of HCC827/ER cells. Further, bufalin + erlotinib significantly reduced the growth of erlotinib-resistant HCC827/ER tumors, induced apoptosis, and inhibited the expression of FGFR and p-ERK proteins. These findings indicated that bufalin could reverse the erlotinib resistance in NSCLC by inhibiting the FGFR expression.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rhein exerts anti-multidrug resistance in acute myeloid leukemia via targeting FTO to inhibit AKT/mTOR. Rhein 通过靶向 FTO 抑制 AKT/mTOR，在急性髓性白血病中发挥抗多药耐药性的作用。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-08-01 Epub Date: 2024-05-07 DOI: 10.1097/CAD.0000000000001608

Shuling Zhang, Lanxia Zhou, Jincai Yang, Jianle Lu, Lili Tao, Youfan Feng, Juan Cheng, Li Zhao

{"title":"Rhein exerts anti-multidrug resistance in acute myeloid leukemia via targeting FTO to inhibit AKT/mTOR.","authors":"Shuling Zhang, Lanxia Zhou, Jincai Yang, Jianle Lu, Lili Tao, Youfan Feng, Juan Cheng, Li Zhao","doi":"10.1097/CAD.0000000000001608","DOIUrl":"10.1097/CAD.0000000000001608","url":null,"abstract":"Chemotherapy failure and resistance are the leading causes of mortality in patients with acute myeloid leukemia (AML). However, the role of m6A demethylase FTO and its inhibitor rhein in AML and AML drug resistance is unclear. Therefore, this study aimed to investigate the antileukemic effect of rhein on AML and explore its potential mechanisms underlying drug resistance. Bone marrow fluid was collected to assess FTO expression in AML. The Cell Counting Kit 8 reagent was used to assess cell viability. Migration assays were conducted to assess the cell migration capacity. Flow cytometry was used to determine the apoptotic effects of rhein and western blot analysis was used to detect protein expression. Online SynergyFinder software was used to calculate the drug synergy scores. The in-vivo antileukemic effect of rhein was assessed in an AML xenograft mouse model. We analyzed different types of AML bone marrow specimens to confirm that FTO is overexpressed in AML, particularly in cases of multidrug resistance. Subsequently, we conducted in-vivo and in-vitro investigations to explore the pharmacological activity and mechanism of rhein in AML and AML with multidrug resistance. The findings demonstrated that rhein effectively suppressed the proliferation and migration of AML cells in a time- and dose-dependent manner and induced apoptosis. Rhein targets FTO, inhibits the AKT/mTOR pathway, and exhibits synergistic antitumor effects when combined with azacitidine. This study elucidates the significant role of FTO and its inhibitor rhein in AML and AML with multidrug resistance, providing new insights for overcoming multidrug resistance in AML.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"597-605"},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140903979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0