Department of Biochemistry, Guangzhou Medical University, Guangzhou, 510182, China.
Mol Biol Rep. 2013 Nov;40(11):6287-93. doi: 10.1007/s11033-013-2741-x. Epub 2013 Sep 24.
Cannabis sativa has 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.
大麻长期以来一直被用作中国的传统药物。其有效成分之一是大麻素。本研究旨在确定合成大麻素 WIN55,212-2（WIN）对 BEL-7402 人肝癌（HCC）细胞系的影响。结果表明，WIN 可降低 BEL-7402 细胞的增殖。此外，WIN 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 活性以及诱导 caspase-3 和多聚 ADP-核糖聚合酶（PARP）的切割，诱导细胞凋亡。WIN 诱导的细胞凋亡伴随着 PPARγ 表达的上调、PPARγ DNA 结合活性的激活以及 PPARγ 靶癌基因 c-myc 的下调。相反，PPARγ 拮抗剂 GW9662 可减弱 WIN 的作用，大麻素受体-2 拮抗剂 AM630 部分减弱 WIN 诱导的 PPARγ 表达，而 GW9662 部分恢复 WIN 诱导的 c-myc 表达降低。总之，我们的研究结果表明，WIN 可通过线粒体 caspase 途径和 PPARγ 介导，降低 BEL-7402 细胞的增殖并诱导其凋亡。这些结果可能为 WIN 在 HCC 治疗中的应用提供依据。
