Anti-Cancer Drugs最新文献

{"title":"Investigation of the synergistic effect mechanism underlying sequential use of palbociclib and cisplatin through integral proteomic and glycoproteomic analysis.","authors":"Lulu Yang, Bo Meng, Xiaoyun Gong, You Jiang, Xuping Shentu, Zhichao Xue","doi":"10.1097/CAD.0000000000001633","DOIUrl":"10.1097/CAD.0000000000001633","url":null,"abstract":"<p><p>Chemoresistance largely hampers the clinical use of chemodrugs for cancer patients, combination or sequential drug treatment regimens have been designed to minimize chemotoxicity and resensitize chemoresistance. In this work, the cytotoxic effect of cisplatin was found to be enhanced by palbociclib pretreatment in HeLa cells. With the integration of liquid chromatography-mass spectrometry-based proteomic and N-glycoproteomic workflow, we found that palbociclib alone mainly enhanced the N-glycosylation alterations in HeLa cells, while cisplatin majorly increased the different expression proteins related to apoptosis pathways. As a result, the sequential use of two drugs induced a higher expression level of apoptosis proteins BAX and BAK. Those altered N-glycoproteins induced by palbociclib were implicated in pathways that were closely associated with cell membrane modification and drug sensitivity. Specifically, the top four frequently glycosylated proteins FOLR1, L1CAM, CD63, and LAMP1 were all associated with drug resistance or drug sensitivity. It is suspected that palbociclib-induced N-glycosylation on the membrane protein allowed the HeLa cell to become more vulnerable to cisplatin treatment. Our study provides new insights into the mechanisms underlying the sequential use of target drugs and chemotherapy drugs, meanwhile suggesting a high-efficiency approach that involves proteomic and N-glycoproteomic to facilitate drug discovery.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619116","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}

{"title":"KLF4 activates LATS2 to promote cisplatin sensitivity in ovarian cancer through DNA damage.","authors":"Ling Ma, Xiaoting Zhao, Xiang Lu, Jiahui Shen, Jiankang Huang","doi":"10.1097/CAD.0000000000001662","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001662","url":null,"abstract":"<p><p>We aimed to investigate the role of large tumor suppressor kinase 2 (LATS2) in cisplatin (DDP) sensitivity in ovarian cancer. Bioinformatic analysis explored LATS2 expression, pathways, and regulators. Quantitative reverse transcription-PCR measured LATS2 and KLF4 mRNA levels. Dual-luciferase and chromatin immunoprecipitation assays confirmed their binding relationship. Cell viability, half maximal inhibitory concentration (IC50) values, cell cycle, and DNA damage were assessed using CCK-8, flow cytometry, and comet assays. Western blot analyzed protein expression. The effect of LATS2 on the sensitivity of ovarian cancer to DDP was verified in vivo. LATS2 and KLF4 were downregulated in ovarian cancer, with LATS2 enriched in cell cycle, DNA replication, and mismatch repair pathways. KLF4, an upstream regulator of LATS2, bound to its promoter. Overexpressing LATS2 increased G1-phase cells, reduced cell viability and IC50 values, and induced DNA damage. Silencing KLF4 alone showed the opposite effect on LATS2 overexpression. Knocking out LATS2 reversed the effects of KLF4 overexpression on cell viability, cell cycle, IC50 values, and DNA damage in ovarian cancer cells. Inhibiting LATS2 inactivated the Hippo-YAP signaling pathway. In vivo experiments showed that overexpression of LATS2 enhanced the sensitivity of ovarian cancer to DDP. KLF4 activates LATS2 via DNA damage to enhance DDP sensitivity in ovarian cancer, providing a potential target for improving treatment outcomes.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374909","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}

{"title":"Research on curcumin mediating immunotherapy of colorectal cancer by regulating cancer associated fibroblasts.","authors":"Chengliang Hou, Yanning Hu, Tao Zhang","doi":"10.1097/CAD.0000000000001659","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001659","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-13","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}

{"title":"MET alterations as resistance mechanisms of dabrafenib-trametinib in BRAF p.V600E mutated non-small cell lung cancer patient.","authors":"Monica Pluchino, Irene Testi, Roberta Minari, Alessandra Dodi, Giulia Airò, Giulia Mazzaschi, Michela Verzè, Alessia Adorni, Letizia Gnetti, Cinzia Azzoni, Costanza Anna Maria Lagrasta, Federica Pecci, Marcello Tiseo","doi":"10.1097/CAD.0000000000001623","DOIUrl":"10.1097/CAD.0000000000001623","url":null,"abstract":"<p><p>The combination of BRAF and MEK inhibitors demonstrated significant clinical benefit in patients with BRAF-mutant non-small cell lung cancer (NSCLC). However, the molecular mechanisms of acquired resistance to BRAF and MEK inhibition in NSCLC are still unknown. Herein, we report a case of a 76-year-old man with a history of smoking who was diagnosed with BRAF V600E-mutant lung adenocarcinoma (PD-L1 > 50%) and subsequently candidate to first-line therapy with pembrolizumab. After 18 months since the start of immunotherapy, computed tomography scan showed disease progression and a second-line therapy with dabrafenib and trametinib was initiated. Seven months later, due to a suspect disease progression, a left supraclavicular lymphadenectomy was performed and next-generation sequencing analysis revealed the appearance of MET exon 14 skipping mutation, while fluorescence in situ hybridization analysis showed MET amplification. The patient is still on BRAF and MEK inhibitor treatment. Our case highlights the relevance of performing tumor tissue rebiopsy at the time of progression during treatment with BRAF/MEK inhibition with the aim of identifying putative mechanisms of resistance.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900781","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}

{"title":"Combination of anlotinib and toripalimab for an advanced biliary tract cancer patient with high Eastern Cooperative Oncology Group performance status: a case report.","authors":"Linger Liu, Baisong Chen, Mengyao Tang, Yinhong Guo, Jili Hou, Wu Zhou, Xiaolian Zhu","doi":"10.1097/CAD.0000000000001619","DOIUrl":"10.1097/CAD.0000000000001619","url":null,"abstract":"<p><p>Up to 80% of biliary tract cancer (BTC) patients relapse within 3 years after surgery and the efficacy of second-line treatment remains dismal for patients who progressed on gemcitabine and cisplatin chemotherapy. Median overall survival of patients with palliative chemotherapy is less than 1 year. The feasibility and safety of targeted therapies plus immunotherapies remain scanty currently, and patients with recurrent or advanced BTCs often experience a rapid decline in Eastern Cooperative Oncology Group (ECOG) performance status. This case report is the first report suggesting a 17-month progression-free survival (PFS), partial response, and another 11-month PFS after progressive disease of anlotinib plus toripalimab in advanced BTC with high ECOG performance status. We report a 67-year-old Chinese male with BTC. He was observed with progressive disease after surgical resection, adjuvant chemotherapy, palliative chemotherapy, and diagnosed with American Joint Committee on Cancer clinical stage IV (cT3N0M1) extrahepatic BTC. The patient experienced a rapid decline in performance status, and he received oral anlotinib and toripalimab with informed consent. MRI scans showed partial response on 22 June 2022. PET-CT showed that tumor activity has been inhibited on 8 March 2023. He achieved 17 months of PFS. Although the patient developed solitary lung metastasis, he had a continuous survival benefit from treatment of anlotinib plus toripalimab after lung radiotherapy. Until the writing of the case draft, he had achieved another 11 months of PFS. The present case suggests that anlotinib plus toripalimab might be a potential effective treatment for advanced BTCs patients with high ECOG performance status.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896935","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}

{"title":"TRIM11 expression levels was downregulated and prevents ferroptosis of cardiomyocyte by Dusp6 in acute myocardial infarction.","authors":"Xiaofu Wu, Wenyuan Zhang","doi":"10.1097/CAD.0000000000001614","DOIUrl":"10.1097/CAD.0000000000001614","url":null,"abstract":"<p><p>Acute myocardial infarction (AMI) is the high incidence rate and mortality of common cardiovascular disease. Herein, we explored the critical role of TRIM11 in AMI and its underlying mechanism. Serum from patients with AMI were collected from our hospital. Mice of model group received angiotensin II. Mice of model + TRIM11 group received with Ang II and TRIM11 vectors. Mice of sham group received normal saline. H9c2 cells were performed transfections using Lipofectamine 2000 (Thermo Fisher Scientific Inc, Shanghai, China), and treated with Ang II. TRIM11 mRNA expression was reduced, was negative correlation with collagen I/III mRNA expression, systolic blood pressure, diastolic blood pressure, left anteroposterior atrial diameter, right atrial diameter, or left ventricular ejection fraction in patient with AMI. TRIM11 mRNA and protein expression were also suppressed. METTL3 regulates TRIM11 methylation to reduce TRIM11 gene stability in model of AMI. TRIM11 gene ameliorated AMI in mice model. TRIM11 gene reduced reactive oxygen species production level of cardiomyocyte in-vitro model. TRIM11 gene reduced ferroptosis of cardiomyocyte in-vitro model. TRIM11 gene reduced ferroptosis by the inhibition of mitochondrial damage of cardiomyocyte in model of AMI. TRIM11 induced Dusp6 protein expression. Bioluminescence imaging showed that TRIM11 virus increased Dusp6 expression in heart tissue of mice model. The inhibition of Dusp6 reduced the effects of TRIM11 on ferroptosis of cardiomyocyte in model of AMI. In conclusion, this study demonstrates that TRIM11 improves AMI by regulating Dusp6 to inhibit ferroptosis of cardiomyocyte, and suggest a novel target for AMI.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890834","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}

{"title":"Icotinib in a lung adenocarcinoma patient with acquired EGFR 19del/C797S mutation-mediated resistance to osimertinib: a case report.","authors":"Fei Cai, Yuanyuan Zhao, Shuxi Song, Dong Zhao, Zhendong Zheng, Long Xu","doi":"10.1097/CAD.0000000000001624","DOIUrl":"10.1097/CAD.0000000000001624","url":null,"abstract":"<p><p>Based on the FLAURA and AURA III trials, compared to first- and second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), osimertinib provides a longer overall survival benefit for patients with untreated EGFR mutated non-small cell lung cancer. Similar to other EGFR-TKIs, drug resistance is, however, inevitable. The most common mechanism of acquired resistance to first-line osimertinib therapy is the C797S mutation, which accounts for 6% of cases. In view of the current challenges of the development of the next generation of EGFR inhibitors, the mechanism of third-generation targeted drug resistances and targeted strategies are key for further exploration. Our case report discusses a female patient with advanced lung adenocarcinoma carrying the EGFR exon19 E746_A750delinsIP mutation who received osimertinib as first-line therapy and acquired C797S resistance during treatment. The patient was then treated with icotinib for 8 months until the disease progressed. Icotinib may be effective in patients with the EGFR 19del-C797S resistant mutation acquired after osimertinib treatment.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287664","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}

{"title":"CDKN2A inhibited ferroptosis through activating JAK2/STAT3 pathway to modulate cisplatin resistance in cervical squamous cell carcinoma.","authors":"Xiang Yong, Yanling Zhang, Heng Tang, Huaiyuan Hu, Rui Song, Qiang Wu","doi":"10.1097/CAD.0000000000001620","DOIUrl":"10.1097/CAD.0000000000001620","url":null,"abstract":"<p><p>Cervical squamous cell carcinoma (CESC) is a significant threat to women's health. Resistance to cisplatin (DDP), a common treatment, hinders the therapeutic efficacy. Understanding the molecular basis of DDP resistance in CESC is imperative. Cyclin-dependent kinase inhibitor 2A (CDKN2A) expression was evaluated through quantitative real-time-PCR and western blot in clinical samples from 30 CESC patients and human cervical epithelial cells and CESC cell lines (SiHa, C33A, and Caski). It was also evaluated through bioinformatics analysis in Timer, Ualcan, and GEPIA database. Cell viability was detected by CCK-8. Apoptosis was detected by Calcein AM/PI assay. Lipid reactive oxygen species (ROS), malondialdehyde, glutathione, Fe 2+ , and iron level were detected by kits. Protein level of JAK2, STAT3, p-JAK2, p-STAT3, ACSL4, GPX4, SLC7A11, and FTL were detected by western blot. In CESC, elevated CDKN2A expression was observed. Cisplatin exhibited a dual effect, inhibiting cell proliferation and inducing ferroptosis in CESC. CDKN2A knockdown in a cisplatin-resistant cell line suppressed proliferation and induced ferroptosis. Moreover, CDKN2A was identified as an inhibitor of erastin-induced ferroptosis. Additionally, targeting the JAK2/STAT3 pathway enhanced ferroptosis in cisplatin-resistant cells. CDKN2A could inhibit ferroptosis in CESC through activating JAK2/STAT3 pathway to modulate cisplatin resistance.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943863","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}

{"title":"Transcriptional regulation of CYR61 and CTGF by LM98: a synthetic YAP-TEAD inhibitor that targets in-vitro vasculogenic mimicry in glioblastoma cells.","authors":"Marie-Eve Roy, Carolane Veilleux, Alexis Paquin, Alexandre Gagnon, Borhane Annabi","doi":"10.1097/CAD.0000000000001627","DOIUrl":"10.1097/CAD.0000000000001627","url":null,"abstract":"<p><p>Glioblastoma (GBM) is a highly angiogenic malignancy of the central nervous system that resists standard antiangiogenic therapy, in part because of an alternative process to angiogenesis termed vasculogenic mimicry. Intricately linked to GBM, dysregulation of the Hippo signaling pathway leads to overexpression of YAP/TEAD and several downstream effectors involved in therapy resistance. Little is known about whether vasculogenic mimicry and the Hippo pathway intersect in the GBM chemoresistance phenotype. This study seeks to investigate the expression patterns of Hippo pathway regulators within clinically annotated GBM samples, examining their involvement in vitro regarding vasculogenic mimicry. In addition, it aims to assess the potential for pharmacological targeting of this pathway. In-silico analysis of the Hippo signaling members YAP1 , TEAD1 , AXL , NF2 , CTGF , and CYR61 transcript levels in low-grade GBM and GBM tumor tissues was done by Gene Expression Profiling Interactive Analysis. Gene expression was analyzed by real-time quantitative PCR from human U87, U118, U138, and U251 brain cancer cell lines and in clinically annotated brain tumor cDNA arrays. Transient gene silencing was performed with specific small interfering RNA. Vasculogenic mimicry was assessed using a Cultrex matrix, and three-dimensional capillary-like structures were analyzed with Wimasis. CYR61 and CTGF transcript levels were elevated in GBM tissues and were further induced when in-vitro vasculogenic mimicry was assessed. Silencing of CYR61 and CTGF , or treatment with a small-molecule TEAD inhibitor LM98 derived from flufenamic acid, inhibited vasculogenic mimicry. Silencing of SNAI1 and FOXC2 also altered vasculogenic mimicry and reduced CYR61 / CTGF levels. Pharmacological targeting of the Hippo pathway inhibits in-vitro vasculogenic mimicry. Unraveling the connections between the Hippo pathway and vasculogenic mimicry may pave the way for innovative therapeutic strategies.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431210","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}

{"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":"<p><p>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.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":null,"pages":null},"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}