桥粒胶蛋白-3介导促卵泡激素通过EGFR/Akt信号通路对卵巢癌细胞增殖活性的调控

目的 通过检测桥粒胶蛋白-3（Dsc3）在卵巢癌中的表达以及促卵泡激素（FSH）对Dsc3、EGFR/Akt信号通路下游分子以及细胞增殖的影响，探讨Dsc3是否介导FSH通过EGFR/Akt信号通路对卵巢癌细胞增殖活性的调控，进而促进肿瘤的发生。方法 免疫组化检测Dsc3在卵巢肿瘤组织中的表达；运用蛋白质印迹分析方法检测Dsc3在6种卵巢肿瘤细胞及卵巢永生化上皮细胞中的表达情况和FSH对Dsc3、EGFR的调控，以及干扰Dsc3、EGFR和应用Akt通路阻断剂对信号通路分子的调控；运用MTT方法检测干扰Dsc3、EGFR以及使用Akt阻断剂后对卵巢癌细胞增殖活性的影响。结果 （1）Dsc3在卵巢癌及交界性卵巢肿瘤中的阳性表达率均高于良性卵巢肿瘤，差异均有统计学意义（P<0.05），Dsc3在卵巢癌中的阳性表达率与交界性卵巢肿瘤的差异无统计学意义（P>0.05）；Dsc3在某些卵巢癌细胞如Hey、HO8910中及交界性卵巢肿瘤细胞MCV152中的表达高于卵巢永生化上皮细胞Moody；（2）FSH呈剂量-时间依赖效应上调Dsc3、EGFR的表达；（3）干扰Dsc3后，信号通路分子EGFR、pAkt受到抑制，Akt无明显改变；干扰EGFR后，信号通路分子Dsc3、pAkt受到抑制，Akt无明显改变；应用Akt通路阻断剂后，Dsc3、pAkt受到抑制，Akt无明显改变；以上三种处理均可抑制FSH对Akt信号通路的调控；（4）干扰Dsc3、EGFR，及应用Akt通路阻断剂均可抑制FSH介导的卵巢癌细胞增殖活性（P<0.05）。结论 Dsc3介导FSH通过EGFR/Akt通路调控的卵巢癌细胞增殖活性，进而促进卵巢癌的发展。

Desmocollin 3 mediates follicle stimulating hormone-induced ovarian epithelial cancer cell proliferation by activating EGFR/Akt signaling pathway

Objective To explore whether desmocollin 3(Dsc3) mediates follicle stimulating hormone(FSH)-induced ovarian epithelial cancer cell proliferation by activating EGFR/Akt signaling pathway, thereby promoting tumor growth. Methods Immunohistochemical staining was used to detect the expression of Dsc3 in ovarian tumor tissues; Western blotting analysis was used to detect Dsc3 protein expression in 6 ovarian tumor cell lines and immortalized ovarian epithelial cells, and Dsc3, EGFR expression after FSH treatment. After knock-down Dsc3 and EGFR expression by siRNA and after treatment with PI3K/Akt signaling pathway inhibitor, Western blotting analysis was used to detect the expression of Dsc3, EGFR, Akt and pAkt; MTT assay was used to determine cellular growth. Results (1) The positive expression rates of Dsc3 in ovarian cancer tissues and borderline ovarian tumor tissues were significantly higher than that in benign ovarian cyst tissues(P<0.05); and the positive rates were similar between the former two tissues. The expression of Dsc3 in some ovarian cancer cells, such as Hey and HO8910 and borderline ovarian tumor cells MCV152, was higher than that in immortalized ovarian epithelial cells (Moody).(2)FSH up-regulated expression of Dsc3 and EGFR in a dose- and time-dependent manner. (3) Inhibition of Dsc3 by RNA interference inhibited the expression of EGFR and pAkt, but not Akt. Inhibition of EGFR by RNA interference inhibited the expression of Dsc3 and pAkt, but not Akt. Inhibition of PI3K/Akt signaling pathway inhibited the expression of Dsc3 and pAkt, but not Akt. The above three methods could all reduce the regulation role of FSH for PI3K/Akt signaling pathway. (4) Inhibition of Dsc3, EGFR and PI3K/Akt signaling pathway could significantly reduce FSH-induced cell proliferation(P<0.05). Conclusion Dsc3 can mediate FSH-induced ovarian epithelial cancer cell proliferation by activating EGFR/Akt signaling pathway, and thereby promoting tumor growth.