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表没食子儿茶素没食子酸酯对人胰腺癌细胞株 PANC-1 细胞增殖及 HIF-1α 和 P-gp 表达的抑制作用。

Inhibitory effects of epigallocatechin-3-gallate on cell proliferation and the expression of HIF-1α and P-gp in the human pancreatic carcinoma cell line PANC-1.

机构信息

Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.

出版信息

Oncol Rep. 2012 May;27(5):1567-72. doi: 10.3892/or.2012.1697. Epub 2012 Feb 22.

Abstract

The aim of this study was to verify the inhibitory effects of epigallocatechin-3-gallate (EGCG) on cell proliferation and the expression of hypoxia-inducible factor 1 (HIF-1α) and multidrug resistance protein 1 (MDR1/P-gp) in the human pancreatic carcinoma cell line PANC-1, thereby, reversing drug resistance of pancreatic carcinoma and improving its sensitivity to cancer chemotherapy. The human pancreatic carcinoma cell line PANC-1 was incubated under hypoxic conditions with different concentrations of epigallocatechin-3-gallate (EGCG) for indicated hours. The effects of EGCG on the mRNA or protein expression of HIF-1α and MDR1 were determined by RT-PCR or western blotting. Cellular proliferation and viability assays were measured using Cell Counting Kit-8. Western blotting revealed that EGCG inhibits the expression of the HIF-1α protein in a dose-dependent manner, while RT-PCR showed that it does not have any effects on HIF-1α mRNA. In addition, EGCG attenuated the mRNA and protein levels of P-gp in a dose-dependent manner, reaching a peak at the highest concentration. Furthermore, EGCG inhibited the proliferation of PANC-1 cells in a concentration- and time-dependent manner. The attenuation of HIF-1α and the consequently reduced P-gp could contribute to the inhibitory effects of EGCG on the proliferation of PANC-1 cells.

摘要

本研究旨在验证表没食子儿茶素没食子酸酯(EGCG)对人胰腺癌细胞系 PANC-1 细胞增殖的抑制作用及其对缺氧诱导因子 1(HIF-1α)和多药耐药蛋白 1(MDR1/P-gp)表达的影响,从而逆转胰腺癌的耐药性,提高其对癌症化疗的敏感性。将人胰腺癌细胞系 PANC-1 在缺氧条件下用不同浓度的表没食子儿茶素没食子酸酯(EGCG)孵育指定时间。通过 RT-PCR 或 Western blot 测定 EGCG 对 HIF-1α 和 MDR1 的 mRNA 或蛋白表达的影响。用细胞计数试剂盒-8 测量细胞增殖和活力。Western blot 显示 EGCG 以剂量依赖性方式抑制 HIF-1α 蛋白的表达,而 RT-PCR 显示其对 HIF-1α mRNA 没有任何影响。此外,EGCG 以剂量依赖性方式减弱 P-gp 的 mRNA 和蛋白水平,在最高浓度时达到峰值。此外,EGCG 以浓度和时间依赖性方式抑制 PANC-1 细胞的增殖。HIF-1α 的衰减和随之而来的 P-gp 的减少可能有助于 EGCG 对 PANC-1 细胞增殖的抑制作用。

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