PPAR gamma mediates the effects of WIN55,212-2, an synthetic cannabinoid, on the proliferation and apoptosis of the BEL-7402 hepatocarcinoma cells
PPAR gamma mediates the effects of WIN55,212-2, an synthetic cannabinoid, on the proliferation and apoptosis of the BEL-7402 hepatocarcinoma cells
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PPAR γ 介导 WIN55,212-2（一种合成大麻素）对 BEL-7402 肝癌细胞增殖和凋亡的影响
DOI：
10.1007/s11033-013-2741-x
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发表时间：
2013
影响因子：
2.8
通讯作者：
Zhao Qing
中科院分区：
文献类型：
--
作者：
Hong Yuehui;Zhou Yuting;Wang Ying;Xiao Shunhua;Liao D. Joshua;Zhao Qing
在中国，大麻一直是一种传统药物。大麻素是其有效成分之一。本研究确定了合成大麻素WIN55,212-2 （WIN）对BEL-7402人肝细胞癌（HCC）细胞系的影响。结果表明，WIN能抑制BEL-7402细胞的增殖。WIN可通过上调Bax表达，下调Bcl-2表达，诱导线粒体膜电位，增加caspase-3、-8和-9活性，诱导caspase-3和聚adp核糖聚合酶（PARP）的裂解，导致细胞凋亡。win诱导的细胞凋亡伴随着PPARγ表达上调、PPARγ DNA结合活性激活、PPARγ靶癌基因c-myc下调。相反，PPARγ拮抗剂GW9662可以减弱WIN的作用，大麻素受体-2拮抗剂AM630可以部分减弱WIN诱导的PPARγ表达，而GW9662可以部分恢复WIN诱导的c-myc表达的降低。综上所述，我们的研究结果表明，WIN可以通过线粒体-caspase途径，通过PPARγ介导，降低BEL-7402细胞的增殖并导致细胞凋亡。这些结果可为WIN在HCC治疗中的应用提供依据。
Cannabis sativahas long been used as a traditional medicine in China. Among its effective compounds are cannabinoids. This study determined the effect of WIN55,212-2 (WIN), a synthetic cannabinoid, on the BEL-7402 human hepatocellular carcinoma (HCC) cell line. The results showed that WIN could decrease the proliferation of BEL-7402 cells. Moreover, WIN could cause apoptosis of the cells via up-regulation of Bax expression, down-regulation of Bcl-2 expression, induction of the mitochondrial membrane potential, increase of caspase-3, -8 and -9 activities, and induction of the cleavage of caspase-3 and poly-ADP-ribose polymerase (PARP). The WIN-induced apoptosis was accompanied by the up-regulation of PPARγ expression, the activation of PPARγ DNA binding activity, and a down-regulation of PPARγ target oncogene c-myc. Conversely, the effects of WIN could be attenuated by PPARγ antagonist GW9662, and the WIN induced PPARγ expression was partially attenuated by AM630, a cannabinoid receptor-2 antagonist, whereas the WIN-induced reduction of c-myc expression was partially restored by GW9662. Collectively, our results suggest that WIN can decrease the proliferation and cause apoptosis of the BEL-7402 cells via a mitochondrial-caspase pathway and mediated by PPARγ. These results may provide a basis for the application of WIN in HCC treatment.