双酚AF诱导乳腺癌细胞增殖的分子机制

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摘要从细胞水平上研究不同浓度双酚AF （BPAF）对MCF-7人乳腺癌细胞系的细胞增殖能力、细胞凋亡、细胞周期等终点的影响；以新型雌激素膜受体GPER1介导的PI3K/Akt和ERK1/2信号通路为靶点，研究低浓度BPAF对该信号通路相关基因表达的影响，以及其在诱导乳腺癌细胞增殖中的作用，评估其增殖效应机制.结果表明，低浓度BPAF （0.001~1μmol/L）能够诱导MCF-7细胞的增殖，使S期细胞比例升高，并且激活雌激素信号通路相关基因mRNA的表达；在较高浓度时（>10μmol/L）能抑制细胞活力，诱导细胞凋亡.通过特异性靶点抑制剂发现GPER1在mRNA层面上激活了PI3K/Akt和ERK1/2信号通路，并且该信号通路的激活可能是BPAF引起MCF-7细胞增殖的关键机制，并且ERα也在其中起到了重要的作用.

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	卢芬
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关键词 ：双酚AF, MCF-7细胞, 细胞增殖, 雌激素信号通路, 分子机制

Abstract：The effects of different concentrations of bisphenol AF (BPAF) on cell viability, cell cycle and apoptosis in MCF-7 In the study, breast cancer cells was evaluated. To evaluate cell proliferation mechanism, the novel estrogen membrane receptor G protein-coupled receptor 1 (GPER1)-mediated phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways were used as targets. The effects of BPAF on the mRNA levels of related targets associated with PI3K/Akt and ERK1/2 signaling pathways were investigated and their roles in low concentration BPAF-induced breast cancer cell proliferation were analyzed. The results showed that low concentrations of BPAF (0.001~1μmol/L) significantly induced the cell proliferation, increased the proportion of S-phase cells and up-regulated mRNA levels of target genes in MCF-7cells. At high concentrations (>10 μmol/L), BPAF significantly inhibited cell viability and induced cell apoptosis. In addition, by using specific signal inhibitors, it was found that GPER1activated PI3K/Akt and ERK1/2 signaling pathways in mRNA level and activation of PI3K/Akt and ERK1/2 signaling pathways via GPER1 may be a key mechanism of BPAF-induced MCF-7 cell proliferation. ERα also plays an important role in this process.

Key words： bisphenol AF MCF-7 cells cell proliferation estrogen signaling pathways molecular mechanism

收稿日期: 2021-04-20

PACS:

X503.1

基金资助:国家自然科学基金资助项目（21507078）

通讯作者: 雷炳莉,副研究员,leibingli@126.com E-mail: leibingli@126.com

作者简介: 卢芬(1985-),女,河南商丘人,讲师,主要从事内科护理学研究,发表论文3篇.

引用本文:

卢芬, 汤倩倩, 娄淑芳, 雷炳莉. 双酚AF诱导乳腺癌细胞增殖的分子机制[J]. 中国环境科学, 2021, 41(12): 5896-5903. LU Fen, TANG Qian-qian, LOU Shu-fang, LEI Bing-li. Molecular mechanism of bisphenol AF-induced proliferation of breast cancer cells. CHINA ENVIRONMENTAL SCIENCECE, 2021, 41(12): 5896-5903.

链接本文:

http://www.zghjkx.com.cn/CN/ 或 http://www.zghjkx.com.cn/CN/Y2021/V41/I12/5896

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