目的探讨内质网应激激活与拓扑异构酶Ⅱα介导的依托泊甙(etoposide,VP16)和放线菌素D(actinomy-cin-D,Act-D)耐药绒癌的关系。方法采用间断诱导法诱导人绒癌细胞系JEG-3,分别建立绒癌ActD耐药细胞系JEG-3/ActDB1和VP16耐药细胞系JEG-3/VPC1。细胞计数法(cell counting kit-8,CCK-8)观察敏感细胞和耐药细胞的生长增殖规律和耐药指数;流式细胞仪检测细胞周期比例和染色体倍性变化;荧光定量PCR技术分别检测两种不同药物诱导的JEG-3耐药株中拓扑异构酶Ⅱα(TopoⅡα)和内质网应激(ERS)各个通路相关的基因mR-NA的表达水平。结果 (1)成功建立了绒癌耐药细胞系JEG-3/ActDB1和JEG-3/VPC1。其耐药指数分别为50.64±10.68和65.87±3.19。耐药株生长速度均较亲本细胞减慢,三者的染色体倍性差异无统计学意义。(2)在两种不同的耐药株中,TopoⅡα的表达水平均明显低于亲本细胞,而与ERS各个通路相关基因均有不同程度的激活。结论成功建立了针对ActD和VP16耐药的绒癌细胞系JEG-3/ActDB1和JEG-3/VPC1。内质网应激激活可能参与绒癌耐药的发生。 Objective To investigate the relationship between endoplasmic reticulum stress activation and topoisomerase Ⅱα-mediated etoposide (VP16) and Actinomycin-D (ACT-D) -treated choriocarcinoma. Methods The human choriocarcinoma cell line JEG-3 was induced by intermittent induction, and JEG-3 / ActDB1 and VP16 cell line JEG-3 / VPC1 were established respectively. Cell counting kit-8 (CCK-8) was used to observe the growth and proliferation of drug-resistant cells and drug resistance index. Flow cytometry was used to detect cell cycle and chromosome ploidy. Fluorescence quantitative PCR The expression of mR-NA in each pathway of topoisomerase Ⅱα (TopoⅡα) and endoplasmic reticulum stress (ERS) in two different drug-induced JEG-3 resistant strains. Results (1) The choriocarcinoma cell lines JEG-3 / ActDB1 and JEG-3 / VPC1 were successfully established. The resistance index was 50.64 ± 10.68 and 65.87 ± 3.19 respectively. The growth rate of resistant strains was slower than that of the parental cells, and there was no significant difference in the ploidy of the three strains. (2) In the two different resistant strains, TopoⅡα expression levels were significantly lower than the parental cells, and ERS pathway-related genes have different degrees of activation. Conclusion The choriocarcinoma cell lines JEG-3 / ActDB1 and JEG-3 / VPC1 resistant to ActD and VP16 were successfully established. Endoplasmic reticulum stress activation may be involved in choriocarcinoma resistance.