醋酸甲羟孕酮和蛋白酶体抑制剂对卵巢癌细胞增殖凋亡的影响

Effects of medroxyprogesterone acetate and proteasome inhibitor on proliferation and apoptosis of ovarian cancer cells

目的:探讨醋酸甲羟孕酮(MPA)和蛋白酶体抑制剂(MG132)对不同孕激素受体(PR)表达卵巢癌细胞增殖、凋亡的影响。方法:CCK-8法检测MPA、MG132单独作用后HO-8910和SKOV3细胞的增殖情况,筛选出合适的药物作用浓度和作用时间。将细胞分为对照组、MPA组、MG132组、MPA+MG132组,采用CCK-8法、流式细胞术检测细胞增殖、凋亡情况;倒置显微镜下观察形态学变化;免疫组化检测PR表达;Western blot检测PR-A、PR-B表达。结果:MPA对HO-8910细胞的增殖抑制作用明显强于SKOV3细胞,而MG132对两种细胞的作用相似。联合用药时,MG132可增强MPA对SKOV3细胞的增殖抑制和诱导凋亡作用,并且伴随着明显的形态学改变,而在HO-8910细胞中不存在此作用。免疫组化及Western blot结果显示,与对照组相比,MG13、MG132+MPA组PR、PR-A和PR-B表达均提升(P<0.05)。结论:MG132可增强MPA对SKOV3细胞增殖抑制和诱导凋亡作用,这可能与PR、PR-A和PR-B表达增加有关。

Objective:To investigate the effects of medroxyprogesterone acetate(MPA)and proteasome inhibitor(MG132)on the proliferation and apoptosis of ovarian cancer cells with different progesterone receptor(PR)expression.Methods:We used CCK-8 assays to detect the proliferation of HO-8910 and SKOV3 cells after MPA,MG132 treated alone,and the appropriate concentration and duration were screened.The cells were divided into 4 groups:Control,MPA,MG132,MPA+MG132.The proliferation and apoptosis were detected by CCK-8 and flow cytometry assays,respectively.The morphological changes were observed by inverted microscope.Immunohistochemistry was used to detect the expression of PR.Western blot was used to detect the expressions of PR-A and PR-B.Results:We found that the antiproliferation effect of MPA on HO-8910 cells was stronger than that of SKOV3 cells,while that of MG132 on both the two cells was similar.The addition of MG132 not only can enhance the antiproliferation and apoptosis effect of MPA on SKOV3 cells,but also significantly decrease the number,change the size and shape of SKOV3 cells,which not happended in HO-8910 cells.The results of immunohistochemistry and Western blot showed that the expressions of PR,PR-A and PR-B were increased in MG132 and MG132+MPA groups compared with the control group(P<0.05).Conclusion:MG132 can enhance sensitivity to MPA on SKOV3 cells,which may be related to the increase of PR,PR-A and PR-B expressions.