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作 者:吴绍梅[1] 张立[1] 王晶 马涛[1] WU Shaomei;ZHANG Li;WANG Jing;MA Tao(Laboratory of Wuxi Maternal and Child Health Hospital,Wuxi 214000,China)
出 处:《西北药学杂志》2022年第1期33-36,共4页Northwest Pharmaceutical Journal
基 金:国家自然科学基金项目(编号:81701635)。
摘 要:目的探究组蛋白去乙酰化酶抑制剂罗米地辛调控卵巢癌细胞顺铂耐药及PD-L1表达的作用。方法体外培养顺铂耐药卵巢癌细胞系COC1/DDP,用CCK-8实验检测细胞活力和顺铂半数抑制质量浓度(IC_(50)),用流式细胞术检测细胞凋亡和PD-L1的表达水平,用实时荧光PCR实验检测细胞PD-L1和STAT3的表达水平,用Western blot检测组蛋白乙酰化水平。结果与Control组相比,Romidepsin组的卵巢癌细胞活力显著下降(P<0.05),IC_(50)值降低,细胞早期凋亡率和晚期凋亡率显著升高(P=0.004、P=0.003),PD-L1 mRNA的表达水平和蛋白表达水平显著升高(P=0.0127),组蛋白H3乙酰化水平显著升高(P<0.0001),STAT3的表达水平显著降低(P=0.0274)。结论Romidepsin可能通过调控组蛋白乙酰化水平和STAT3的表达水平逆转卵巢癌细胞对顺铂的耐药性,促进顺铂诱导细胞凋亡,提高PD-L1的表达水平。Objective To investigate the effects of Romidepsin,a histone deacetylase inhibitor,on the regulation of cisplatin resistance and PD-L1 expression in ovarian cancer cells.Methods Cis-platin resistant ovarian cancer cell line COC1/DDP was cultured in vitro,and the cell viability and cis-platin half maximal inhibitory concentration value(IC_(50))were detected by CCK-8 assay;cell apoptosis and PD-L1 expression were detected by flow cytometry.The expression levels of PD-L1 and STAT3 were detected by real-time PCR.The level of histone acetylation was determined by Western blot.Results Compared with the control group,the ovarian cancer cells viability in Romidepsin group decreased significantly(P<0.05),the IC_(50) value was reduced,the early apoptosis and late apoptosis rate increased significantly(P=0.004,P=0.003),the PD-L1 mRNA expression levels and protein expression levels significantly increased(P=0.0127),the histone H3 acetylation levels increased significantly(P<0.0001),and STAT3 expression level decreased significantly(P=0.0274).Conclusion Romidepsin may reverse cisplatin resistance in ovarian cancer cells by regulating the acetylation level of histone and the expression of STAT3,promote cis-platin-induced cell apoptosis and increase the expression of PD-L1.
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