Quercetin inhibits breast cancer cell proliferation and survival by targeting Akt/mTOR/PTEN signaling pathway

IF 3.2 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ji Jiang, Yan Yang, Fuhuan Wang, Wei Mao, Zhongjun Wang, Zegang Liu
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Abstract

Recently, natural compounds such as quercetin have gained an increasing amount of attention in treating breast cancer. However, the exact mechanisms responsible for the antiproliferative functions of quercetin are not completely understood. Therefore, we aimed to examine quercetin impacts on breast cancer cell proliferation and survival and the involvement of PI3K/Akt/mTOR pathway. Breast cancer MDA-MB-231 and MCF-7 cells were exposed to quercetin, and cell proliferation was assessed by MTT assay. ELISA was applied to evaluate cell apoptosis. The expression levels of apoptotic mediators such as caspase-3, Bcl-2, Bax and PI3K, Akt, mTOR, and PTEN were assessed via qRT-PCR and western blot. We found that quercetin suppressed dose dependently cell growth capacity in MDA-MB-231 and MCF-7 cells. In addition, quercetin treatment increase apoptosis in both cells lines via modulating the pro- and antiapoptotic markers. Quercetin upregulated PTEN and downregulated PI3K, Akt, and mTOR, hence suppressing this signaling pathway in cells. In conclusion, we showed antiproliferative and pro-apoptotic function of quercetin in breast cancer cell lines, which is mediated by targeting and suppressing PI3K/Akt/mTOR signal transduction.

Abstract Image

Abstract Image

槲皮素通过靶向 Akt/mTOR/PTEN 信号通路抑制乳腺癌细胞的增殖和存活。
最近,槲皮素等天然化合物在治疗乳腺癌方面受到越来越多的关注。然而,槲皮素抗增殖功能的确切机制尚未完全明了。因此,我们旨在研究槲皮素对乳腺癌细胞增殖和存活的影响以及 PI3K/Akt/mTOR 通路的参与。将乳腺癌 MDA-MB-231 和 MCF-7 细胞暴露于槲皮素,用 MTT 法评估细胞增殖。采用 ELISA 法评估细胞凋亡。通过 qRT-PCR 和 Western 印迹评估了细胞凋亡介质如 caspase-3、Bcl-2、Bax 和 PI3K、Akt、mTOR 和 PTEN 的表达水平。我们发现,槲皮素对MDA-MB-231和MCF-7细胞生长能力的抑制具有剂量依赖性。此外,槲皮素还能通过调节促凋亡和抗凋亡标志物增加细胞凋亡。槲皮素能上调 PTEN,下调 PI3K、Akt 和 mTOR,从而抑制细胞中的这一信号通路。总之,我们发现槲皮素在乳腺癌细胞系中具有抗增殖和促凋亡功能,而这是通过靶向和抑制PI3K/Akt/mTOR信号转导介导的。
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来源期刊
Chemical Biology & Drug Design
Chemical Biology & Drug Design 医学-生化与分子生物学
CiteScore
5.10
自引率
3.30%
发文量
164
审稿时长
4.4 months
期刊介绍: Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.
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