PLAC8在子宫内膜癌中的表达及其调控癌细胞增殖和凋亡的机制

Expression of PLAC8 in endometrial carcinoma and its mechanism of regulating cancer cell proliferation and apoptosis

目的探讨胎盘特异性蛋白8(PLAC8)在子宫内膜癌中的表达及其调控癌细胞凋亡的机制。方法采用免疫组织化学法检测PLAC8在子宫内膜癌组织中的表达水平,分析PLAC8表达与患者临床病理参数、患者生存时间的关系。构建敲低PLAC8表达的Ishikawa细胞株,采用MTT试验检测细胞增殖能力,流式细胞仪检测细胞凋亡情况,Western-blot检测细胞中AKT、pAKT、mTOR和pmTOR蛋白的表达。结果与正常子宫内膜组织比较,PLAC8在子宫内膜癌组织中的表达明显上调(P<0.05)。PLAC8高表达与肿瘤级别高、国际妇产科协会(FIGO)分期为Ⅲ~Ⅳ期和Ki67增殖指数>50相关,PLAC8高表达的患者比PLAC8低表达患者生存时间要短(P<0.05)。敲低PLAC8表达能明显抑制细胞增殖、促进细胞凋亡、抑制pAKT和pmTOR蛋白的表达(P<0.05)。结论子宫内膜癌中PLAC8呈高表达,敲低PLAC8表达能促进癌细胞的凋亡,其机制可能是通过调控AKT/mTOR信号通路起作用。

Objective To investigate the expression of placenta specific 8(PLAC8)in endometrial cancer and its mechanism of regulating cancer cell apoptosis.Methods Immunohistochemistry was used to detect the expression level of PLAC8 in endometrial cancer tissues and the relationship between the expression of PLAC8 and the patients′clinicopathological parameters and patients′survival time was analyzed.The Ishikawa cell line that knocked down the expression of PLAC8 was constructed,the cell proliferation ability was detected by MTT experiment,apoptosis was detected by flow cytometry,and the expression of AKT,pAKT,mTOR and pmTOR protein in the cells was detected by Western-blot.Results Compared with adjacent tissues,the expression of PLAC8 in endometrial cancer tissues was significantly up-regulated(P<0.05).High expression of PLAC8 was positively correlated with high tumor grade,FIGO stageⅢ-Ⅳand Ki67 proliferation index>50.Patients with high expression of PLAC8 had a shorter survival time than patients with low expression of PLAC8(P<0.05).Decreasing the expression of PLAC8 could significantly inhibit cell proliferation,promote cell apoptosis,and inhibit the expression of pAKT and pmTOR protein(P<0.05).Conclusion PLAC8 is highly expressed in endometrial cancer.Decreasing the expression of PLAC8 can promote the apoptosis of cancer cells.The mechanism is to regulate the AKT/mTOR signaling pathway.