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白藜芦醇通过缺氧诱导因子 1-α(HIF-1α)/活性氧(ROS)/P53 信号通路诱导小鼠前列腺癌细胞凋亡。

Resveratrol Induces Apoptosis in Murine Prostate Cancer Cells via Hypoxia-Inducible Factor 1-alpha (HIF-1α)/Reactive Oxygen Species (ROS)/P53 Signaling.

机构信息

Department of Urology Surgery, The Affiliated Zhongshan Hospital Dalian University, Dalian, Liaoning, China (mainland).

Department of Urology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China (mainland).

出版信息

Med Sci Monit. 2018 Dec 11;24:8970-8976. doi: 10.12659/MSM.913290.

Abstract

BACKGROUND Resveratrol, a polyphenol found on the surface of red fruits, is able to suppress many kinds of malignancies. Nevertheless, its mechanism of action is not yet clear. Consequently, this study aimed to elucidate its influence and explore the etiology of PCCs (prostate cancer cells). MATERIAL AND METHODS The proliferation of prostate cancer cells was determined by CCK-8 assay. Cell apoptosis was determined by Hoechst staining FC assay. Cell migration was detected by scratch test. The levels of apoptosis-related protein were detected by Western blot analysis. RESULTS It was discovered that resveratrol suppresses cellular survival and migration and enhances cell death. In addition, it was revealed that resveratrol elevated ROS concentration and expression of biomarker of cell death Bax, while inhibiting Bcl2, an anti-apoptotic protein, and reinforcing expression of p53. Moreover, resveratrol remarkably increased the expressions of HIF-1α and p53 in PC cells. Resveratrol suppressed cell survival and promoted cell death, but its effects were reversed after HIF-1α knockdown, suggesting that the effects of resveratrol in PC are mediated via HIF-1α. CONCLUSIONS Our findings indicate that resveratrol induces apoptosis via HIF-1α/ROS/p53 signaling in prostate cancer cells and may be a useful therapeutic agent against prostate cancer.

摘要

背景

白藜芦醇是一种存在于红色水果表面的多酚,能够抑制多种恶性肿瘤。然而,其作用机制尚不清楚。因此,本研究旨在阐明其影响,并探讨 PCCs(前列腺癌细胞)的病因。

材料与方法

通过 CCK-8 检测法测定前列腺癌细胞的增殖情况。通过 Hoechst 染色 FC 检测法测定细胞凋亡情况。通过划痕试验检测细胞迁移情况。通过 Western blot 分析检测凋亡相关蛋白的水平。

结果

发现白藜芦醇抑制细胞存活和迁移,促进细胞死亡。此外,白藜芦醇还能提高 ROS 浓度和细胞死亡标志物 Bax 的表达,同时抑制抗凋亡蛋白 Bcl2,并增强 p53 的表达。此外,白藜芦醇在 PC 细胞中显著增加了 HIF-1α 和 p53 的表达。白藜芦醇抑制细胞存活并促进细胞死亡,但在 HIF-1α 敲低后其作用被逆转,表明白藜芦醇在 PC 中的作用是通过 HIF-1α 介导的。

结论

我们的研究结果表明,白藜芦醇通过 HIF-1α/ROS/p53 信号通路诱导前列腺癌细胞凋亡,可能是治疗前列腺癌的一种有用的治疗剂。

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