孕激素对不同PGRMC2表达的卵巢癌细胞迁移、侵袭的影响及发生机制

Effects of progesterone on migration and invasion in different PGRMC2-expressing ovarian cancer cells and related mechanism

目的探讨孕激素对不同孕激素受体膜成分2(progesterone receptor membrane component 2,PGRMC2)表达的卵巢癌细胞迁移、侵袭的影响以及发生机制。方法体外应用不同浓度孕激素对SKOV3(PGRMC2低表达)、HO-8910(PGRMC2高表达)两株卵巢癌细胞进行干预。每株细胞均分4组:对照组(0μmol/L)、实验组(10、20、40μmol/L)。运用CCK-8法检测SKOV3、HO-8910细胞增殖情况;Transwell迁移和侵袭实验检测SKOV3、HO-8910细胞转移能力和侵袭能力;Western blot法检测SKOV3、HO-8910细胞的PGRMC2、β-catenin蛋白表达。结果CCK-8结果显示,孕激素可抑制卵巢癌细胞的增殖,呈浓度-时间依赖性降低,且对HO-8910细胞抑制增殖的作用较SKOV3细胞明显(P<0.05)。Transwell迁移、侵袭实验结果显示,孕激素相同浓度及时间作用下,SKOV3细胞转移能力较HO-8910细胞强,且细胞的转移能力均随着孕激素浓度的升高而降低(P<0.05)。此外,Western blot法结果显示,HO-8910、SKOV3细胞中实验组的PGRMC2蛋白表达与对照组相比,差异无统计学意义(P>0.05),但HO-8910细胞PGRMC2蛋白表达明显高于SKOV3细胞(P<0.05)。与对照组相比,两细胞株各实验组的β-catenin蛋白表达呈降低趋势(P<0.05)。结论孕激素可能通过PGRMC2介导下调Wnt/β-catenin信号通路的活性,从而影响卵巢癌SKOV3、HO-8910细胞迁移、侵袭能力。

Purpose To investigate the effects and related mechanism of progesterone(P)on the migration and invasion of ovarian cancer cells expressed by different progesterone receptor membrane component 2(PGRMC2).Methods In vitro application of different concentrations of progesterone to SKOV3(low expression of PGRMC2),HO-8910(high expression of PGRMC2)two ovarian cancer cells were intervened.Each cell was divided into 4 groups:control group(0μmol/L)and experimental group(10,20,40μmol/L).The proliferation of SKOV3 and HO-8910 cells was detected by CCK-8 method,the migration ability of SKOV3 and HO-8910 cells was detected by Transwell migration assay,the invasive ability of SKOV3 and HO-8910 cells was detected by Transwell invasion assay,and the expression of PGRMC2 andβ-catenin protein on SKOV3 and HO-8910 cells were detected by Western blot.Results The results of CCK-8 showed that progesterone inhibited the proliferation of ovarian cancer cells in a concentration-time-dependent manner,and the effect of inhibiting proliferation of HO-8910 cells was significantly higher than that of SKOV3 cells(P<0.05).Transwell migration and invasion experiments showed that the metastasis ability of SKOV3 cells was stronger than that of HO-8910 cells under the same concentration and time of progesterone,and the metastasis ability of cells decreased with the increase of progesterone concentration(P<0.05).In addition,Western blot results showed that the expression of PGRMC2 protein in HO-8910 and SKOV3 cells was not significantly different from that in the control group(P>0.05),but the expression of PGRMC2 protein in HO-8910 cells was significantly higher than that in SKOV3 cells(P<0.05).Compared with the control group,the expression ofβ-catenin protein in each experimental group of the two cell lines showed a decreasing trend(P<0.05).Conclusion Progesterone may down-regulate the activity of Wnt/β-catenin signaling pathway through PGRMC2,which may affect the migration and invasion of ovarian cancer SKOV3 and HO-8910 cells.