Formononetin induces the mitochondrial apoptosis pathway in prostate cancer cells via downregulation of the IGF-1/IGF-1R signaling pathway
Formononetin induces the mitochondrial apoptosis pathway in prostate cancer cells via downregulation of the IGF-1/IGF-1R signaling pathway
复制标题
芒柄花素通过下调 IGF-1/IGF-1R 信号通路诱导前列腺癌细胞线粒体凋亡通路
DOI：
10.3109/13880209.2013.842600
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发表时间：
2014-04-01
影响因子：
3.8
通讯作者：
Ye, Yu
中科院分区：
文献类型：
--
作者：
Huang, Wen-Jun;Bi, Ling-Yun;Ye, Yu
摘要背景：芒柄花素，一种抗肿瘤药物，可以抑制癌细胞的增殖，包括前列腺癌细胞。然而，其抗肿瘤机制仍不清楚。目的：目的探讨芒柄花素对前列腺癌细胞的抗肿瘤作用是否与胰岛素样生长因子1（IGF-1）/胰岛素样生长因子1受体（IGF-1 R）信号通路有关。材料与方法：采用MTT法检测芒柄花素（25、50和100 μM）处理PC-3细胞48 h后细胞活力的变化。Hoechst 33258染色和流式细胞术检测福莫奈汀诱导的细胞凋亡。实时荧光定量PCR检测Bax mRNA的表达，Western blot检测Bax和IGF-1 R蛋白的表达水平。结果：芒柄花素在浓度>12.5 μM时对人前列腺癌细胞增殖有明显的抑制作用。芒柄花素可剂量依赖性地增加Bax mRNA和蛋白表达水平，降低pIGF-1 R蛋白表达水平。结论：高浓度芒柄花素通过抑制IGF-1/IGF-1 R途径诱导雄激素非依赖性前列腺癌细胞凋亡
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.