Anti-Cancer Drugs最新文献_第5页

Research on curcumin mediating immunotherapy of colorectal cancer by regulating cancer associated fibroblasts. 姜黄素通过调节癌症相关成纤维细胞介导结直肠癌免疫疗法的研究。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2025-01-01 Epub Date: 2024-10-17 DOI: 10.1097/CAD.0000000000001659

Chenliang Hou, Yanning Hu, Tao Zhang

{"title":"Research on curcumin mediating immunotherapy of colorectal cancer by regulating cancer associated fibroblasts.","authors":"Chenliang Hou, Yanning Hu, Tao Zhang","doi":"10.1097/CAD.0000000000001659","DOIUrl":"10.1097/CAD.0000000000001659","url":null,"abstract":"The objective was to investigate curcumin's (Cur) function and associated molecular mechanisms in regulating tumor immunity in colon cancer. Primary cancer-associated fibroblasts (CAFs) from mouse CT26 colon cancer tumors were isolated. Validation of primary CAFs using immunofluorescence assay was done. Cell Counting Kit-8 experiments, real-time quantitative PCR (qPCR), and enzyme linked immunosorbent assay experiments were conducted to investigate how curcumin affected the growth and cytokine secretion functions of CAFs. The effect of curcumin on regulating PD-L1 expression on CT26 cells through CAFs in vitro was explored through coculture of CAFs and tumor cells, qPCR, and western blot experiments. A mouse colon cancer cell model was established in Balb/c nude mice to explore the effect of curcumin on colon tumor cells. Changes in the tumor microenvironment were detected by flow cytometry to explore the synergistic effect of curcumin combined with anti-PD-1 monoclonal antibody in the treatment of mouse colon cancer. In vitro, curcumin prevented the growth and TGF-β secretion of CT26 cells. At the same time, curcumin inhibited the secretion of TGF-β by CAFs, thereby downregulating the PD-L1 expression of CT26 cells. In vivo, curcumin combined with anti-PD-1 antibodies can further enhance the inhibitory effect of PD-1 antibodies on tumors and increase the number of tumor-suppressing immune cells in the tumor microenvironment, such as M1 macrophages and CD8 T cells, thus inhibiting tumors. Immune M2 macrophages, regulatory T cells, and other cells were reduced. In conclusion, curcumin reduces the expression of PD-L1 in colon cancer cells and improves the tumor immune microenvironment by inhibiting the proliferation of CAFs and the secretion of TGF-β. Curcumin and anti-PD-1 treatment have synergistic inhibitory effects on colon cancer.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"72-78"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279600","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

Synergistic combination effect of the PCA-1/ALKBH3 inhibitor HUHS015 on prostate cancer drugs in vitro and in vivo. PCA-1/ALKBH3 抑制剂 HUHS015 在体外和体内对前列腺癌药物的协同组合效应。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2025-01-01 Epub Date: 2024-08-26 DOI: 10.1097/CAD.0000000000001656

Miyuki Mabuchi, Kazutake Tsujikawa, Akito Tanaka

{"title":"Synergistic combination effect of the PCA-1/ALKBH3 inhibitor HUHS015 on prostate cancer drugs in vitro and in vivo.","authors":"Miyuki Mabuchi, Kazutake Tsujikawa, Akito Tanaka","doi":"10.1097/CAD.0000000000001656","DOIUrl":"10.1097/CAD.0000000000001656","url":null,"abstract":"Prostate cancer antigen-1/ALKBH3, a DNA/RNA demethylase of 3-methylcytosine, 1-methyladenine (1-meA), and 6-meA, was found in prostate cancer as an important prognostic factor. Additionally, 1-meA has been associated with other cancers. The ALKBH3 inhibitor HUHS015 was found to be effective against prostate cancer both in vitro and in vivo . Herein, we investigated the effect of HUHS015 in combination with drugs for prostate cancer approved in Japan (including bicalutamide, cisplatin, mitoxantrone, prednisolone, ifosfamide, tegafur/uracil, docetaxel, dacarbazine, and estramustine) by treating DU145 cells with around IC 50 value concentrations of these drugs for 3 days. Additionally, the cells were observed for additional 9 days after drug removal. Combination treatment with dacarbazine, estramustine, tegafur/uracil, and HUHS015 showed a slight additive effect after 3 days. After drug washout of them and mitoxantrone, the combined effects and levels were enhanced and sustained, although the effects of each treatment alone declined. HUHS015 combined with cisplatin or docetaxel elicited synergistic and sustained effects. In vivo , combining HUHS015 and docetaxel, the first chemotherapeutic agent for castration-resistant prostate cancer, showed notable effects in the DU145 xenograft model. In conclusion, HUHS015 exhibited a synergistic effect with docetaxel and drugs acting on DNA in vitro , even after drug removal. Since cancer chemotherapy is typically administered during rest periods due to its high toxicity, combining it with an ALKBH3 inhibitor could be a promising strategy for enhancing cancer treatment, as it can elicit an additive effect during treatment, allowing dosage reduction, and synergistically sustain the effect after drug washout during rest periods.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"19-27"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279601","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

Holding the therapy in CLLp53: mechanisms to achieve durable responses. 在 CLLp53 中坚持治疗：实现持久应答的机制。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2025-01-01 Epub Date: 2024-08-09 DOI: 10.1097/CAD.0000000000001653

Rodrigo Cantera, Tatiana Fernández-Barge, Jon Salmanton-García, Lucrecia Yáñez

引用次数: 0

Machine learning-based integration develops a multiple programmed cell death signature for predicting the clinical outcome and drug sensitivity in colorectal cancer. 基于机器学习的整合开发出一种多程序细胞死亡特征，用于预测结直肠癌的临床结果和药物敏感性。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2025-01-01 Epub Date: 2024-08-09 DOI: 10.1097/CAD.0000000000001654

Chunhong Li, Yuhua Mao, Yi Liu, Jiahua Hu, Chunchun Su, Haiyin Tan, Xianliang Hou, Minglin Ou

{"title":"Machine learning-based integration develops a multiple programmed cell death signature for predicting the clinical outcome and drug sensitivity in colorectal cancer.","authors":"Chunhong Li, Yuhua Mao, Yi Liu, Jiahua Hu, Chunchun Su, Haiyin Tan, Xianliang Hou, Minglin Ou","doi":"10.1097/CAD.0000000000001654","DOIUrl":"10.1097/CAD.0000000000001654","url":null,"abstract":"Tumorigenesis and treatment are closely associated with various programmed cell death (PCD) patterns. However, the coregulatory role of multiple PCD patterns in colorectal cancer (CRC) remains unknown. In this study, we developed a multiple PCD index (MPCDI) based on 19 PCD patterns using two machine learning algorithms for risk stratification, prognostic prediction, construction of nomograms, immune cell infiltration analysis, and chemotherapeutic drug sensitivity analysis. As a result, in the TCGA-COAD, GSE17536, and GSE29621 cohorts, the MPCDI can effectively distinguished survival outcomes in CRC patients and served as an independent factor for CRC patients. We then explored the immune infiltration landscape in two groups using the nine algorithms and found more overall immune infiltration in the high-MPCDI group. TIDE scores suggested that the increased immune evasion potential and immune checkpoint inhibition therapy may be less effective in the high-MPCDI group. Immunophenoscores indicated that anti-PD1, anti-cytotoxic T-lymphocyte associated antigen 4 (anti-CTLA4), and anti-PD1-CTLA4 combination therapies are less effective in the high-MPCDI group. In addition, the high-MPCDI group was more sensitive to AZD1332, Foretinib, and IGF1R_3801, and insensitive to AZD3759, AZD5438, AZD6482, Erlotinib, GSK591, IAP_5620, and Picolinici-acid, which suggests that the MPCDI can guide drug selection for CRC patients. As a new clinical classifier, the MPCDI can more accurately distinguish CRC patients who benefit from immunotherapy and develop personalized treatment strategies for CRC patients.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"1-18"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915974","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

Pathological complete response achieved with FLOT chemotherapy in two patients with MSI-H esophagogastric junction and gastric adenocarcinoma. 两名 MSI-H 型食管胃交界处和胃腺癌患者接受 FLOT 化疗后获得病理完全缓解。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2025-01-01 Epub Date: 2024-08-09 DOI: 10.1097/CAD.0000000000001652

Federica Cosso, Daniele Lavacchi, Luca Messerini, Vittorio Briganti, Francesca Castiglione, Marco Brugia, Valentina Berti, Sara Fancelli, Fabio Cianchi, Agnese Vannini, Serena Pillozzi, Lorenzo Antonuzzo

{"title":"Pathological complete response achieved with FLOT chemotherapy in two patients with MSI-H esophagogastric junction and gastric adenocarcinoma.","authors":"Federica Cosso, Daniele Lavacchi, Luca Messerini, Vittorio Briganti, Francesca Castiglione, Marco Brugia, Valentina Berti, Sara Fancelli, Fabio Cianchi, Agnese Vannini, Serena Pillozzi, Lorenzo Antonuzzo","doi":"10.1097/CAD.0000000000001652","DOIUrl":"10.1097/CAD.0000000000001652","url":null,"abstract":"Globally, more than 1 million new cases of gastric cancer were estimated in 2020, ranking fourth in cancer mortality. Currently although in resectable gastric cancer and esophagogastric junction (EGJ) adenocarcinoma a perioperative triplet chemotherapy regimen including a fluoropyrimidine, a platinum compound and docetaxel (FLOT) demonstrated a better overall survival, the survival rate is still very low, and a massive effort is still required to improve clinical prognosis. High microsatellite instability (MSI-H) status in gastric cancer is a favorable prognostic factor but poor data are available on its predictive role for perioperative FLOT chemotherapy in resectable gastric cancer. Here, we presented the case of two patients with advanced MSI-H gastric cancer/EGJ adenocarcinoma who had no residual tumor following neoadjuvant FLOT chemotherapy maintaining a complete response for more than 30 months, suggesting MSI-H status to be a positive prognostic marker also in patients treated with a taxane-containing triplet in this setting. We also discuss the future perspectives including the opportunity to achieve excellent clinical outcomes with immune checkpoint inhibitor (ICI)-based regimens.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"85-88"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905674","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

EP-0108A is a moderation selectively BRD4 BD2 inhibitor with potential AML tumor suppression. EP-0108A 是一种适度选择性 BRD4 BD2 抑制剂，具有抑制急性髓细胞性白血病肿瘤的潜力。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2025-01-01 Epub Date: 2024-08-28 DOI: 10.1097/CAD.0000000000001655

Li Li, Hui Zhu, Shuang Liu

{"title":"EP-0108A is a moderation selectively BRD4 BD2 inhibitor with potential AML tumor suppression.","authors":"Li Li, Hui Zhu, Shuang Liu","doi":"10.1097/CAD.0000000000001655","DOIUrl":"10.1097/CAD.0000000000001655","url":null,"abstract":"Acute myeloid leukemia is the most common type of acute leukemia in adults. The epigenetic molecule BRD4 is a member of the bromodomain and extra-terminal family and plays an important role in the occurrence and development of tumors. BRD4 is essential for oncogene expression, including c-Myc. So, BRD4 inhibition is considered as an effective strategy for the treatment of hematological and solid malignancies. In recent years, several small molecule inhibitors targeting BRD4 have been developed. However, these inhibitors had excessive hematological toxicity due to the lack of specific binding to BD1 and BD2 domains of BRD4, while other inhibitors with high selectivity lose their antitumor efficacy. To balance the relationship between efficacy and safety, we developed EP-0108A, a BRD4 inhibitor with moderate selectivity for the BD2 domain over BD1 domain of BRD4. Our results show that EP-0108A has antitumor effects in MV4-11 and Kasumi-1 cell line-derived xenograft mouse models without significant effects on heart or breathing safe in rats and Beagle dogs. In repeated dose toxicity studies, EP-0108A showed reversible hematological and gastrointestinal toxicity in both rats and dogs. Our findings indicate that EP-0108A has the potential to be a new therapeutic agent for the treatment of cancer.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"28-38"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279599","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

Utidelone plus pembrolizumab as the fourth-line combination treatment in non-small cell lung cancer with EGFR mutation: a case report. 表皮生长因子受体（EGFR）突变的非小细胞肺癌四线联合治疗病例报告：优替龙联合 pembrolizumab。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2025-01-01 Epub Date: 2024-10-18 DOI: 10.1097/CAD.0000000000001661

Henghu Fang, Wei Yang, Qing Han, Rugang Zhao, Wei Zheng, Zejun Lu, Shanshan Wu, Qi Zhu, Jingjiao Li, Gaowa Guan, Juyi Wen

{"title":"Utidelone plus pembrolizumab as the fourth-line combination treatment in non-small cell lung cancer with EGFR mutation: a case report.","authors":"Henghu Fang, Wei Yang, Qing Han, Rugang Zhao, Wei Zheng, Zejun Lu, Shanshan Wu, Qi Zhu, Jingjiao Li, Gaowa Guan, Juyi Wen","doi":"10.1097/CAD.0000000000001661","DOIUrl":"10.1097/CAD.0000000000001661","url":null,"abstract":"Utidelone is an ebomycin derivative chemotherapeutic drug, which can promote tubulin polymerization and stabilize microtubule structure, so as to induce apoptosis. The drug is an innovative drug independently developed by China with independent intellectual property rights. Phase II clinical trials for advanced breast cancer are being approved by National Medical Products Administration for the treatment of advanced breast cancer. However, there is no report on the application in non-small cell lung cancer (NSCLC) patients with the epidermal growth factor receptor (EGFR) mutation. This case is a patient with EGFR mutant stage IV NSCLC who has progressed after third-line targeted therapy. The fourth line was treated with utidelone combined with pabolizumab. The patient had progressed after targeted therapy with oxitinib, ametinib, and vometinib. Due to the patient's physical reasons, the traditional platinum drugs were not suitable, so the patient was treated with utidelone combined with pabolizumab. The curative effect was evaluated as SD after two cycles and progesterone receptor after four cycles. At present, it is still in the maintenance of reduction of utidelone combined with pabolizumab, and the tumor continues to shrink. Although peripheral neurotoxicity occurred during treatment, it improved after symptomatic treatment. The treatment of EGFR mutant stage IV NSCLC with utidelone combined with pabolizumab has good effect and mild adverse reactions.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"94-96"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456487","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

DEPDC1 affects autophagy-dependent glycolysis levels in human osteosarcoma cells by modulating RAS/ERK signaling through TTK. DEPDC1通过TTK调节RAS/ERK信号，从而影响人骨肉瘤细胞中依赖自噬的糖酵解水平。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-11-01 Epub Date: 2024-07-15 DOI: 10.1097/CAD.0000000000001643

Dong Yu, Lin Chen, Yingchun Li, Bailian Liu, Weiping Xiao

{"title":"DEPDC1 affects autophagy-dependent glycolysis levels in human osteosarcoma cells by modulating RAS/ERK signaling through TTK.","authors":"Dong Yu, Lin Chen, Yingchun Li, Bailian Liu, Weiping Xiao","doi":"10.1097/CAD.0000000000001643","DOIUrl":"10.1097/CAD.0000000000001643","url":null,"abstract":"The current treatment for osteosarcoma (OS) is based on surgery combined with systemic chemotherapy, however, gene therapy has been hypothesized to improve patient survival rates. The density-enhanced protein domain 1 protein (DEPDC1) functions as a crucial determinant in the advancement of OS, which is highly expressed in OS cells. The current study was designed to delve into the effect and mechanism of DEPDC1 and phosphotyrosine-picked threonine tyrosine kinase (TTK) in OS. The expression of DEPDC1 and TTK in OS cells was detected by western blotting. Furthermore, the assessment of glycolysis encompassed the quantification of extracellular acidification rate, glucose uptake rate, lactate concentration, and the expression of glucose transporter 1, hexokinase 2, and pyruvate kinase M2. Finally, the functions of DEPDC1 and TTK in autophagy and ras-extracellular signal-regulated kinase signaling were determined by western blotting after interfering with DEPDC1 in SaOS-2 cells. The results revealed that DEPDC1 and TTK were upregulated in OS cell lines and interfering with DEPDC1 inhibited glycolysis and autophagy in OS cells. Furthermore, the STRING database suggested that DEPDC1 and TTK perform targeted binding. Notably, the results of the present study revealed that DEPDC1 upregulated RAS expression through TTK and enhanced ERK activity, thereby affecting glycolysis and autophagy in OS cells. Collectively, the present investigation demonstrated that DEPDC1 affected autophagy-dependent glycolysis levels of OS cells by regulating RAS/ERK signaling through TTK.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"893-901"},"PeriodicalIF":1.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625792","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

Differential functionality of fluoropyrimidine nucleosides for safe cancer therapy. 氟嘧啶核苷的不同功能可安全治疗癌症。

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-11-01 Epub Date: 2024-08-20 DOI: 10.1097/CAD.0000000000001644

Tim Holzinger, Julia Frei, Natalia Teresa Jarzebska, Hans-Dietmar Beer, Thomas M Kündig, Steve Pascolo, Severin Läuchli, Mark Mellett

{"title":"Differential functionality of fluoropyrimidine nucleosides for safe cancer therapy.","authors":"Tim Holzinger, Julia Frei, Natalia Teresa Jarzebska, Hans-Dietmar Beer, Thomas M Kündig, Steve Pascolo, Severin Läuchli, Mark Mellett","doi":"10.1097/CAD.0000000000001644","DOIUrl":"10.1097/CAD.0000000000001644","url":null,"abstract":"Chemotherapies are standard care for most cancer types. Pyrimidine analogs including 5-fluorouracil, cytosine arabinoside, 5-azacytidine, and gemcitabine are effective drugs that are utilized as part of a number of anticancer regimens. However, their lack of cell-specificity results in severe side effects. Therefore, there is a capacity to improve the efficacy of such therapies, while decreasing unwanted side effects. Here, we report that while 5-fluorocytosine is not chemotherapeutic in itself, incorporated into a ribonucleoside and more importantly into an RNA oligonucleotide, it induces cytotoxic effects on cancer cells in vitro . Interestingly, these effects are rescued by both uridine and thymidine. Similarly, in-vitro 2'-deoxy-5-fluorocytidine inhibits the growth of tumor cells but has the advantage of being less toxic to human primary cells compared with 5-fluorocytidine, suggesting that the deoxyribonucleoside could exhibit less side-effects in vivo . Thus, this work indicates that the potency of 5-fluorocytidine and 2'-deoxy-5-fluorocytidine should be further explored. In particular, oligonucleotides incorporating 5-fluorocytosine could be novel chemotherapeutic drugs that could be formulated in cancer-specific particles for safe and efficacious cancer treatments.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"912-921"},"PeriodicalIF":1.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625793","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

Upregulation of CDC25B by transcription factor TEAD4 drives invasion and inhibits cisplatin sensitivity through cell adhesion in stomach adenocarcinoma. 转录因子 TEAD4 对 CDC25B 的上调通过细胞粘附作用驱动胃腺癌的侵袭并抑制顺铂敏感性

IF 1.8 4区医学

Anti-Cancer Drugs Pub Date : 2024-11-01 Epub Date: 2024-07-22 DOI: 10.1097/CAD.0000000000001645

Tao Zhang, Lijian Chen, Shuang Li, Chao Shen

{"title":"Upregulation of CDC25B by transcription factor TEAD4 drives invasion and inhibits cisplatin sensitivity through cell adhesion in stomach adenocarcinoma.","authors":"Tao Zhang, Lijian Chen, Shuang Li, Chao Shen","doi":"10.1097/CAD.0000000000001645","DOIUrl":"10.1097/CAD.0000000000001645","url":null,"abstract":"Cisplatin is crucial in management of advanced stomach adenocarcinoma, whereas development of chemotherapy resistance hinders overall efficacy of cisplatin. This work aims to explore role of CDC25B in cisplatin sensitivity in stomach adenocarcinoma and offer a possible mechanism for explaining its function. By using bioinformatics approaches, CDC25B and TEAD4 expression levels in stomach adenocarcinoma tissues and enriched pathways of CDC25B were analyzed. qRT-PCR of CDC25B and TEAD4 expression in stomach adenocarcinoma cells, CCK-8 detection of cell viability and IC 50 values, and colony formation assay on cell proliferation were performed. Cell adhesion experiment detected cell adhesion ability. Western blot detected expression of proteins related to cell adhesion, specifically Muc-1, ICAM-1, VCAM-1. Dual luciferase assay and ChIP experiment verified binding relationship between TEAD4 and CDC25B. CDC25B was upregulated in stomach adenocarcinoma tissues and cells, enriched in focal adhesion pathway. Treatment with cell adhesion inhibitors revealed that CDC25B overexpression inhibits the sensitivity of stomach adenocarcinoma to cisplatin through the cell adhesion pathway. CDC25B has an upstream transcription factor TEAD4, which targeted and bound to CDC25B and was highly expressed in stomach adenocarcinoma. Rescue experiment revealed that knocking down TEAD4 weakened suppressive impact of CDC25B overexpression on sensitivity of stomach adenocarcinoma cells to cisplatin. Transcription factor TEAD4 could activate the transcription of CDC25B through cell adhesion to drive cell invasion and reduce sensitivity of stomach adenocarcinoma to cisplatin. TEAD4 and CDC25B may become new targets for management of stomach adenocarcinoma.","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"922-931"},"PeriodicalIF":1.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854565","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