卵巢癌中E2通过ERα降低顺铂敏感性的研究

发布时间：2018-03-16 11:07

本文选题：卵巢癌　切入点：雌激素受体α　出处：《东南大学学报(医学版)》2017年03期 　论文类型：期刊论文

【摘要】：目的:探讨顺铂治疗的卵巢癌中铂抵抗与雌激素受体(ERα)及17β-雌二醇(E2)之间的关系。方法:以卵巢癌细胞系Caov-3和Ovcar-3作为研究模型,分别给予不同药物处理,并设计ERα-siRNA对ERα进行下调,研究在不同处理方式下卵巢癌细胞的增殖及凋亡水平,同时分析顺铂对ERα磷酸化、蛋白激酶B(Akt)和细胞外信号调节蛋白激酶(ERK)的调节。结果:在卵巢癌细胞中,E2通过ERα促进细胞增殖,并降低卵巢癌细胞对顺铂的敏感性;ER拮抗剂ICI 182780(ICI)可以增强卵巢癌细胞对顺铂的敏感性;顺铂通过激活ERK诱导ERα的磷酸化,其磷酸化位点为丝氨酸118;下调ERα后,E2对顺铂细胞毒性的拮抗作用降低,且经E2处理后,卵巢癌细胞的抗凋亡蛋白Bcl-2表达上调,细胞的凋亡降低。结论:卵巢癌中,ERα在顺铂抵抗中扮演重要角色,E2通过诱导ERα激活并降低凋亡,进而降低顺铂的细胞毒性。因此在铂抗性卵巢癌的治疗中,ERα可能是一个潜在的治疗靶标。
[Abstract]:Objective: to investigate the relationship between platinum resistance and estrogen receptor ER 伪 and 17 尾 -estradiol E _ 2 in ovarian cancer treated with cisplatin. Methods: ovarian cancer cell lines Caov-3 and Ovcar-3 were treated with different drugs. ER 伪 -siRNA was designed to down-regulate ER 伪, to study the proliferation and apoptosis of ovarian cancer cells under different treatments, and to analyze the phosphorylation of ER 伪 by cisplatin. Regulation of protein kinase (BK) and extracellular signal-regulated protein kinase (ERK). Results: in ovarian cancer cells, E _ 2 promotes cell proliferation through ER 伪. The ER antagonist ICI 182780 can enhance the sensitivity of ovarian cancer cells to cisplatin, and cisplatin induces the phosphorylation of ER 伪 by activating ERK. The phosphorylation site was serine 118, the antagonistic effect of E _ 2 on cisplatin cells was decreased after down-regulation of ER 伪, and the expression of anti-apoptotic protein Bcl-2 was up-regulated in ovarian cancer cells after treatment with E _ 2. Conclusion: ER 伪 plays an important role in cisplatin resistance by inducing ER 伪 activation and decreasing apoptosis. Therefore, ER 伪 may be a potential therapeutic target in the treatment of platinum-resistant ovarian cancer.
【作者单位】：长治医学院药学系;中国人民解放军火箭军总医院;
【分类号】：R737.31

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