Huang Zhiwei, Wang Lianqiu, Chen Lifeng, Zhang Yifei, Shi Ping
Acta Pharm. 2015 Dec;65(4):463-71. doi: 10.1515/acph-2015-0034.
Clioquinol has been shown to have anticancer activity in several carcinoma cells. In this study, we preliminarily examined the effect of clioquinol in human SMMC-7721 hepatoma and QSG-7701 normal hepatic cells. Our results indicated that clioquinol did not significantly affect survival of QSG-7701 cells, whereas it reduced cell viability in a concentration- and time-dependent manner in SMMC-7721 cells. Clioquinol did not trigger autophagy and apoptosis, while it induced cell cycle arrest in the S-phase in SMMC- 7721 cells. Additionally, down-regulation of cyclin D1, A2, E1, Cdk2 and up-regulation of p21, p27 were detected after the treatment with clioquinol. The results demonstrated for the first time that clioquinol suppressed cell cycle progression in the S-phase in SMMC-7721 cells via the p21, p27-cyclin E,A/Cdk2 pathway. This suggests that clioquinol may have a therapeutic potential as an anticancer drug for certain malignances.
氯碘羟喹已被证明在多种癌细胞中具有抗癌活性。在本研究中，我们初步检测了氯碘羟喹对人SMMC - 7721肝癌细胞和QSG - 7701正常肝细胞的作用。我们的结果表明，氯碘羟喹对QSG - 7701细胞的存活率没有显著影响，而在SMMC - 7721细胞中，它以浓度和时间依赖性方式降低细胞活力。氯碘羟喹不会引发自噬和凋亡，但会诱导SMMC - 7721细胞的细胞周期阻滞于S期。此外，用氯碘羟喹处理后，检测到细胞周期蛋白D1、A2、E1、细胞周期蛋白依赖性激酶2（Cdk2）表达下调，p21、p27表达上调。结果首次证明，氯碘羟喹通过p21、p27 - 细胞周期蛋白E、A/细胞周期蛋白依赖性激酶2途径抑制SMMC - 7721细胞的S期细胞周期进程。这表明氯碘羟喹作为一种抗癌药物对某些恶性肿瘤可能具有治疗潜力。
