本文關(guān)鍵詞： 自噬 子宮內(nèi)膜癌 G蛋白偶聯(lián)受體　出處：《中國(guó)生物化學(xué)與分子生物學(xué)報(bào)》2017年04期 　論文類型：期刊論文

【摘要】：雌激素是子宮內(nèi)膜癌發(fā)生發(fā)展的重要誘導(dǎo)因子,但關(guān)于其在子宮內(nèi)膜癌中的作用機(jī)制目前仍不明確。自噬對(duì)細(xì)胞的存活具有重要的調(diào)節(jié)作用,研究發(fā)現(xiàn)其在子宮內(nèi)膜癌發(fā)生發(fā)展的過(guò)程中起重要的調(diào)節(jié)作用。本文通過(guò)探討雌激素對(duì)子宮內(nèi)膜癌細(xì)胞自噬的影響,深入地了解雌激素促進(jìn)子宮內(nèi)膜發(fā)展的機(jī)制,并明確GPR30-AMPK-mT OR通路在其中的作用。MTT及透視電鏡的結(jié)果顯示,雌激素可以誘導(dǎo)細(xì)胞的自噬及增強(qiáng)細(xì)胞的活力,而這種作用具有一定的時(shí)間及濃度依賴性。同時(shí),蛋白質(zhì)印跡及實(shí)時(shí)定量PCR結(jié)果顯示雌激素可以促進(jìn)LC3、p-AMPK的表達(dá),并且抑制P62、pmT OR的表達(dá),表明雌激素可以激活A(yù)MPK/mT OR通路。沉默G蛋白偶聯(lián)受體30(GPR30)后,結(jié)果顯示雌激素誘導(dǎo)細(xì)胞的自噬及細(xì)胞活力的作用被逆轉(zhuǎn),并且可以抑制AMPK/mT OR通路的激活,而G-1結(jié)果與之相反,表明雌激素通過(guò)GPR30激活A(yù)MPK/mT OR通路,誘導(dǎo)自噬及細(xì)胞活力。此外,加入AMPK抑制劑compound C,可以抑制雌激素誘導(dǎo)細(xì)胞的自噬及細(xì)胞活力的能力,并且促進(jìn)P62、p-mT OR表達(dá),降低LC3及p-AMPK表達(dá),表明雌激素通過(guò)激活A(yù)MPK/mT OR激活細(xì)胞自噬及增強(qiáng)細(xì)胞活力。同時(shí)細(xì)胞預(yù)先加入自噬抑制劑3-MA或轉(zhuǎn)染ATG5siRNA,可以降低雌激素增強(qiáng)細(xì)胞的活力,表明雌激素通過(guò)誘導(dǎo)自噬增強(qiáng)細(xì)胞活力。綜合以上結(jié)果,雌激素通過(guò)GPR30-AMPK-mT OR通路誘導(dǎo)細(xì)胞的自噬增強(qiáng)細(xì)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.
【作者單位】： 樂(lè)山市市中區(qū)人民醫(yī)院病理科;廣州醫(yī)科大學(xué)附屬惠州醫(yī)院(惠州市第三人民醫(yī)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)~~
【分類號(hào)】：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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