米非司酮对人耐药卵巢癌细胞增殖、凋亡及其对紫杉醇敏感性的影响

Effects of mifepristone on the proliferation,apoptosis,and taxol sensitivity of drug-resistant human ovarian cancer cells

背景与目的:米非司酮是有效的孕酮受体拮抗剂。研究发现,米非司酮对体内外卵巢癌细胞均具有生长抑制作用,但机制尚不清楚。本研究旨在探讨米非司酮对人耐药卵巢癌细胞A2780/T增殖、凋亡及其对紫杉醇敏感性的影响,为临床应用米非司酮治疗耐药性卵巢癌提供实验依据。方法:体外培养人卵巢癌耐药细胞A2780/T,采用CCK-8法检测单用米非司酮及合用紫杉醇时对A2780/T细胞增殖的影响,分析米非司酮与紫杉醇在抑制耐药卵巢癌细胞增殖中的相互作用。采用流式细胞术分析米非司酮及米非司酮联合紫杉醇对A2780/T细胞凋亡的影响。结果:实验所选各种浓度(0.625～20μg/mL)米非司酮对A2780/T和A2780细胞均有一定程度的生长抑制作用,并呈浓度依赖性。当紫杉醇浓度为1.25或2.5μg/mL,合用米非司酮浓度为20、10、5、2.5、1.25或0.625μg/mL时,能显著抑制A2780/T细胞的增殖,并显示两种药物的协同作用(q>1.15)。当紫杉醇浓度为0.625或5μg/mL时,仅表现为两种药物的相加作用(0.85<q<1.15)。米非司酮可诱导A2780/T细胞凋亡。当米非司酮浓度为1.25、2.5和5μg/mL时,细胞凋亡率分别为(15.50±1.48)%、(26.28±0.76)%和(45.13±0.91)%。当以上3种浓度米非司酮与2.5μg/mL紫杉醇联合作用时,显示了两种药物在诱导A2780/T细胞凋亡作用上的协同效应。结论:米非司酮能够显著抑制人卵巢癌细胞A2780/T和A2780增殖,诱导A2780/T细胞凋亡,并能增强A2780/T细胞对紫杉醇的敏感性。

Background and purpose：Mifepristone is an effective progesterone receptor antagonist.It was reported that mifepristone can inhibit the growth of ovarian carcinoma cells either in vitro or in vivo,but the exact mechanism is unknown.The purpose of this study was to investigate the effect of mifepristone on the proliferation,apoptosis,and taxol sensitivity of taxol-resistant human ovarian cancer cells,and to give experimental basis for treating refractory ovarian cancer with mifepristone.Methods：Taxol-resistant human ovarian cancer cell line A2780/T cells were cultured in vitro,and the CCK-8 assay was used to examine the antiproliferative effect of mifepristone with or without taxol on A2780/T cells.The cooperative effects between mifepristone and taxol in inhibiting the growth of A2780/T cells were analyzed.Flow cytometry（FCM） was used to examine the effects of mifepristone with or without taxol on the apoptosis.Results：Mifepristone produced concentration-dependent antiproliferative effect on A2780/T cells at all experimental concentrations（0.625–20 μg/mL）.Enhanced antiproliferative effects were found when A2780/T cells were cultured with mifepristone at 20,10,5,2.5,1.25 and 0.625 μg/mL combined with 1.25 or 2.50 μg/mL taxol（q1.15）.Only additive effects were found when the cells were cultured with mifepristone and 0.625 or 5 μg/mL taxol（0.85q1.15）.Mifepristone induced apoptosis in A2780/T cells.The apoptosis rates were（15.50±1.48）%,（26.28±0.76）% and（45.13±0.91）%,when the cells were cultured with mifepristone at 1.25,2.5 and 5 μg/mL,respectively.Synergic effect of mifepristone（at 5,2.5,1.25 μg/mL） combined with 2.5 μg/mL taxol was found in inducing A2780/T cells apoptosis.Conclusion：Mifepristone can inhibit the growth of taxol-resistant human ovarian cancer cells,induce apoptosis,and enhance its taxol sensitivity.