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大豆苷元通过下调IGF-1/IGF-1R信号通路诱导前列腺癌细胞的线粒体凋亡途径。

Formononetin induces the mitochondrial apoptosis pathway in prostate cancer cells via downregulation of the IGF-1/IGF-1R signaling pathway.

作者信息

Huang Wen-Jun, Bi Ling-Yun, Li Zhen-Zhao, Zhang Xing, Ye Yu

机构信息

Department of Emergency, First Affiliated Hospital of Guangxi Medical University , Nanning , China .

出版信息

Pharm Biol. 2013 Dec 20. doi: 10.3109/13880209.2013.842600.

DOI:10.3109/13880209.2013.842600
PMID:24359236
Abstract

Abstract Context: Formononetin, an isoflavone, can inhibit the proliferation of cancer cells, including those of the prostate. However, its antitumor mechanism remains unclear. Aim: To investigate whether the insulin-like growth factor 1 (IGF-1)/insulin-like growth factor 1 receptor (IGF-1 R) signaling pathway mediates the formononetin antitumor effect on prostate cancer cells. Materials and methods: The viability of PC-3 cells was measured by MTT assay 48 h after formononetin treatment (25, 50 and 100 μM). Formononetin-induced cell apoptosis was measured by Hoechst 33258 staining and flow cytometry. Expression of Bax mRNA was detected by real-time PCR, and the expression levels of Bax and IGF-1 R proteins were detected by western blots. Results: At concentrations >12.5 μM, formononetin significantly inhibited the proliferation of human prostate cancer cells. Formononetin increased Bax mRNA and protein expression levels and decreased the expression levels of pIGF-1 R protein in a dose-dependent manner. Conclusion: High concentrations of formononetin-induced apoptosis in androgen-independent prostate cancer cells through inhibition of the IGF-1/IGF-1 R pathway.

摘要

摘要 背景:大豆苷元,一种异黄酮,能够抑制癌细胞的增殖,包括前列腺癌细胞。然而,其抗肿瘤机制仍不清楚。目的:研究胰岛素样生长因子1(IGF-1)/胰岛素样生长因子1受体(IGF-1R)信号通路是否介导大豆苷元对前列腺癌细胞的抗肿瘤作用。材料与方法:用MTT法检测大豆苷元(25、50和100μM)处理48小时后PC-3细胞的活力。用Hoechst 33258染色和流式细胞术检测大豆苷元诱导的细胞凋亡。通过实时PCR检测Bax mRNA的表达,通过蛋白质印迹法检测Bax和IGF-1R蛋白的表达水平。结果:浓度>12.5μM时,大豆苷元显著抑制人前列腺癌细胞的增殖。大豆苷元以剂量依赖的方式增加Bax mRNA和蛋白表达水平,并降低pIGF-1R蛋白的表达水平。结论:高浓度大豆苷元通过抑制IGF-1/IGF-1R途径诱导雄激素非依赖性前列腺癌细胞凋亡。

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