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首页> 美国卫生研究院文献>Brazilian Journal of Medical and Biological Research >Rhein induces apoptosis of human gastric cancer SGC-7901 cells via an intrinsic mitochondrial pathway
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Rhein induces apoptosis of human gastric cancer SGC-7901 cells via an intrinsic mitochondrial pathway

机译：大黄酸通过内在的线粒体途径诱导人胃癌SGC-7901细胞凋亡

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摘要

Rhein is a primary anthraquinone found in the roots of a traditional Chinese herb, rhubarb, and has been shown to have some anticancer effects. The aim of the present study was to investigate the effect of rhein on the apoptosis of the human gastric cancer line SGC-7901 and to identify the mechanism involved. SGC-7901 cells were cultured and treated with rhein (0, 50, 100, 150, and 200 µM) for 24, 48, or 72 h. Relative cell viability assessed by the MTT assay after treatment was 100, 99, 85, 79, 63% for 24 h; 100, 98, 80, 51, 37% for 48 h, and 100, 97, 60, 36, 15% for 72 h, respectively. Cell apoptosis was detected with TUNEL staining and quantified with flow cytometry using annexin FITC-PI staining at 48 h after 100, 200 and 300 µm rhein. The percentage of apoptotic cells was 7.3, 21.9, 43.5%, respectively. We also measured the mRNA levels of caspase-3 and -9 using real-time PCR. Treatment with 100 µM rhein for 48 h significantly increased mRNA expression of caspase-3 and -9. The levels of apoptosis-related proteins including Bcl-2, Bax, Bcl-xL, and pro-caspase-3 were evaluated in rhein-treated cells. Rhein increased the Bax:Bcl-2 ratio but decreased the protein levels of Bcl-xL and pro-caspase-3. Moreover, rhein significantly increased the expression of cytochrome c and apoptotic protease activating factor 1, two critical components involved in mitochondrial pathway-mediated apoptosis. We conclude that rhein inhibits SGC-7901 proliferation by inducing apoptosis and this antitumor effect of rhein is mediated in part by an intrinsic mitochondrial pathway.
机译：大黄酸是在传统中草药大黄的根中发现的主要蒽醌，并已显示出一定的抗癌作用。本研究的目的是研究大黄酸对人胃癌SGC-7901细胞凋亡的影响并确定其机制。培养SGC-7901细胞并用大黄酸（0、50、100、150和200μm）处理24、48或72μh。处理24 h后，通过MTT分析评估的相对细胞存活率为100％，99％，85％，79％，63％；对于48 h，分别为100％，98％，80％，51％，37％，对于72 h，分别为100％，97％，60％，36％，15％。用100μl，200μm和300μm的大黄酸处理后48 h，用TUNEL染色检测细胞凋亡，并用膜联蛋白FITC-PI染色，通过流式细胞术进行定量。凋亡细胞的百分比分别为7.3、21.9、43.5％。我们还使用实时PCR测量了caspase-3和-9的mRNA水平。用100µµM大黄酸处理48µh可以显着增加caspase-3和-9的mRNA表达。在大黄酸处理的细胞中评估了凋亡相关蛋白的水平，包括Bcl-2，Bax，Bcl-xL和caspase-3。大黄酸增加了Bax：Bcl-2的比率，但降低了Bcl-xL和pro-caspase-3的蛋白质水平。此外，大黄酸显着增加了细胞色素c和凋亡蛋白酶激活因子1的表达，这是线粒体途径介导的细胞凋亡中的两个关键成分。我们得出的结论是，大黄酸通过诱导细胞凋亡来抑制SGC-7901的增殖，而大黄酸的这种抗肿瘤作用部分是由固有的线粒体途径介导的。

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