广州医药2025，Vol.56Issue(10)：1363-1371,9.DOI:10.20223/j.cnki.1000-8535.2025.10.006
GSDME对SKOV-3卵巢癌细胞化疗耐药的影响
Effect of GSDME on chemoresistance in ovarian cancer
摘要
Abstract
Objective To explore whether drug resistance in ovarian cancer is associated with gasdermin E(GSDME)methylation,and to explore whether decitabine can reverse ovarian cancer chemoresistance by increasing GSDME protein expression levels through demethylation.Methods The cisplatin-resistant cell line(SKOV-3/DDP)was constructed by inverse concentration gradient of cisplatin.Semi-inhibitory concentration(IC50)of cell lines after drug resistance was detected using the CCK8 assay.Real-time fluorescence quantitative methylation-specific PCR was used to detect the methylation level of GSDME gene in the two groups of cells.Wetern Blot was used to detect the expression level of GSDME in the two groups of cells.Drug-resistant cell lines were treated with different concentrations of the demethylating drug decitabine.Experiments above were repeated to detect the methylation degree of IC50 and GSDME genes and the expression level of GSDME protein in drug-resistant cells before and after decitabine treatment.Results Compared with SKOV-3 cells,the methylation level of GSDME gene in SKOV-3/DDP was significantly increased(P＜0.01),while the expression level of GSDME protein was significantly decreased(P＜0.001).With the increase of decitabine concentration,the methylation degree of GSDME gene in drug-resistant cells was gradually decreased,the expression level of protein was gradually increased,and the IC50 of cells was gradually decreased:the methylation level of GSDME gene was decreased after 0.05 μg/mL decitabine treatment(P＜0.01),but there were no significant changes in protein expression level and IC50 of drug-resistant cells(P＞0.05).The protein expression level was significantly increased when the concentration of local citabine was increased to 0.10 μg/mL(P＜0.05),while the IC50 of the cells was not significantly decreased(P＞0.05).When the drug concentration reached 0.15 μg/mL,the IC50 of the cells showed a significant downward trend(P＜0.05).Conclusions The expression of GSDME is closely related to chemoresistance in ovarian cancer,and the low expression of GSDME due to its high methylation level can promote chemoresistance in ovarian cancer.However,decitabine can increase the expression level of GSDME in drug-resistant ovarian cancer cells through demethylation,thereby increasing the sensitivity of ovarian cancer cells to chemotherapeutic drugs,and then reversing the chemoresistance of ovarian cancer.关键词
卵巢癌/焦孔素E/化疗耐药/地西他滨/甲基化Key words
ovarian cancer/GSDME/chemoresistant/cisplatin/methylation引用本文复制引用
张渊,白芷玉,李琪,闫俐嘉,贾娟蓉,冯勤梅,尹海珍..GSDME对SKOV-3卵巢癌细胞化疗耐药的影响[J].广州医药,2025,56(10):1363-1371,9.基金项目
山西省基础研究计划(202103021224387) （202103021224387）
