雌激素通过GPR30-AMPK-mTOR通路诱导Ishikawa细胞自噬增强细胞活力（英文）

发布时间：2018-01-25 22:14

本文关键词： 自噬子宫内膜癌 G蛋白偶联受体　出处：《中国生物化学与分子生物学报》2017年04期 　论文类型：期刊论文

【摘要】：雌激素是子宫内膜癌发生发展的重要诱导因子,但关于其在子宫内膜癌中的作用机制目前仍不明确。自噬对细胞的存活具有重要的调节作用,研究发现其在子宫内膜癌发生发展的过程中起重要的调节作用。本文通过探讨雌激素对子宫内膜癌细胞自噬的影响,深入地了解雌激素促进子宫内膜发展的机制,并明确GPR30-AMPK-mT OR通路在其中的作用。MTT及透视电镜的结果显示,雌激素可以诱导细胞的自噬及增强细胞的活力,而这种作用具有一定的时间及浓度依赖性。同时,蛋白质印迹及实时定量PCR结果显示雌激素可以促进LC3、p-AMPK的表达,并且抑制P62、pmT OR的表达,表明雌激素可以激活AMPK/mT OR通路。沉默G蛋白偶联受体30(GPR30)后,结果显示雌激素诱导细胞的自噬及细胞活力的作用被逆转,并且可以抑制AMPK/mT OR通路的激活,而G-1结果与之相反,表明雌激素通过GPR30激活AMPK/mT OR通路,诱导自噬及细胞活力。此外,加入AMPK抑制剂compound C,可以抑制雌激素诱导细胞的自噬及细胞活力的能力,并且促进P62、p-mT OR表达,降低LC3及p-AMPK表达,表明雌激素通过激活AMPK/mT OR激活细胞自噬及增强细胞活力。同时细胞预先加入自噬抑制剂3-MA或转染ATG5siRNA,可以降低雌激素增强细胞的活力,表明雌激素通过诱导自噬增强细胞活力。综合以上结果,雌激素通过GPR30-AMPK-mT OR通路诱导细胞的自噬增强细胞的活力。
[Abstract]:Estrogen is an important inducing factor in the development of endometrial carcinoma, but the mechanism of estrogen in endometrial carcinoma is still unclear. Autophagy plays an important role in regulating cell survival. It has been found that estrogen plays an important role in the development of endometrial carcinoma. In this paper, the effects of estrogen on autophagy of endometrial cancer cells were studied. To understand the mechanism of estrogen promoting the development of endometrium, and to clarify the role of GPR30-AMPK-mT OR pathway in it. Estrogen can induce autophagy and enhance cell viability in a time-and concentration-dependent manner. Western blotting and real-time quantitative PCR showed that estrogen could promote the expression of LC3p-AMPK and inhibit the expression of P62pmT OR. The results showed that estrogen could activate the AMPK/mT OR pathway. After silencing G-protein-coupled receptor 30 (GPR30), the results showed that the effects of estrogen on autophagy and cell viability were reversed. It also inhibited the activation of AMPK/mT OR pathway, whereas G-1 showed that estrogen activates AMPK/mT OR pathway through GPR30. In addition, the addition of AMPK inhibitor compound C could inhibit the ability of estrogen to induce autophagy and cell viability, and promote P62. The expression of p-mT OR decreased the expression of LC3 and p-AMPK. These results suggest that estrogen activates autophagy and enhances cell viability by activating AMPK/mT OR. At the same time, the cells are pretreated with autophagy inhibitor 3-MA or transfected with ATG5siRNA. Estrogen can reduce the activity of the cells, suggesting that estrogen enhances the viability of the cells by inducing autophagy. Estrogen induces autophagy through GPR30-AMPK-mT OR pathway to enhance cell viability.
【作者单位】：乐山市市中区人民医院病理科;广州医科大学附属惠州医院(惠州市第三人民医院)病理科;
【基金】：Supported by National Natural Science Foundation of China(No.81600342) Science and Technology Program of Guangdong(No.A2014810;No.A2015620)~~
【分类号】：R737.33
【正文快照】： Endometrial carcinoma is one of gynecologic malignancies,and its incidence in China has recently increased,which is influenced by environment,diet,and the use of hormonal drugs such as estrogens[1].We now know that estrogen plays an important role in the

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