Triptolide-induced cell cycle arrest and apoptosis in human renal cell carcinoma cells
Triptolide-induced cell cycle arrest and apoptosis in human renal cell carcinoma cells
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雷公藤内酯醇诱导人肾细胞癌细胞的细胞周期停滞和细胞凋亡。
DOI：
10.3892/or.2011.1158
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发表时间：
2011-04-01
期刊：
影响因子：
4.2
通讯作者：
Yan, Guangmei
中科院分区：
文献类型：
--
作者：
Li, Jingjie;Zhu, Wenbo;Yan, Guangmei
肾细胞癌（RCC）是最常见的类型的肾脏起源的恶性肿瘤。虽然肾切除术成功地用于挽救局部RCC患者的生命，但晚期和其他难治性RCC的治疗效果较差，仍然不足。在这里，我们表明，雷公藤内酯醇，一个小分子和众所周知的抗炎和抗免疫剂在临床上使用，是能够诱导细胞凋亡通过线粒体途径在786-0 RCC细胞系。这种诱导与线粒体稳定相关的基因如Bcl-2和Bcl-X-L的表达减少一致。细胞周期分析显示，雷公藤甲素作用后G 0/G1和G2/M期细胞比例减少，S期细胞比例增加。细胞在S期的积累可归因于细胞周期检查点调节因子如细胞周期蛋白A、细胞周期蛋白B、CDK 1、CDK 2和视网膜母细胞瘤蛋白（Rb）的表达减少。这些结果提高了雷公藤内酯醇诱导的细胞凋亡是由细胞周期阻滞介导的可能性。类似地，在另一个人RCC细胞系中。OS RC 2、雷公藤内酯醇诱导细胞凋亡及S期细胞聚集。因此，雷公藤内酯醇通过影响细胞增殖和凋亡的协调调节而成为细胞凋亡的刺激物，并可能适用于人肾癌的治疗。
Renal cell carcinoma (RCC) is the most frequent type of renal-originated malignancy. Although nephrectomy is successfully used to save the lives of patients with localized RCC, treatment of advanced and other refractory RCCs is poor and still inadequate. Here, we show that triptolide, a small molecule and a well-known anti-inflammatory and anti-immunity agent used in the clinic, is capable of inducing cell apoptosis via the mitochondrial pathway in the 786-0 RCC cell line. This induction occurred in concert with reduced expression of genes related to the stabilization of mitochondria such as Bcl-2 and Bcl-X-L. Cell cycle analysis showed that exposure to triptolide decreased the proportion of cells in the G0/G1 and G2/M phases, and increased the proportion of cells in the S phase. Cell accumulation in the S phase can be attributed to reduced expression of cell cycle checkpoint regulators such as cyclin A, cyclin B, CDK1, CDK2 and retinoblastoma proteins (Rb). These results raise the possibility that triptolide-induced apoptosis is mediated by cell cycle arrest. Similarly, in another human RCC cell line. OS-RC-2, triptolide-induced apoptosis and cell accumulation in S phase were also observed. Therefore, triptolide emerges as a stimulator of apoptosis by influencing coordinate regulation of proliferation and apoptosis, and may be applicable to the treatment of human renal cell carcinoma.