丙戊酸钠通过线粒体凋亡通路诱导肝癌细胞凋亡

背景：已经有人发现丙戊酸钠可以抑制成神经细胞瘤以及其他一些肿瘤细胞的细胞增殖。丙戊酸钠对肝癌细胞的的增殖抑制作用在近期也被人发现，但是具体机制还不清楚。本研究是为了证实丙戊酸钠对肝癌细胞的增殖抑制作用以及其具体机制。 方法：用WST法和克隆形成抑制来检测丙戊酸钠对肝癌细胞的增殖抑制作用，hoechest 33258染色来检测细胞核形态的改变，流式细胞仪检测丙戊酸钠诱导的肝癌细胞凋亡率，JNK, p-JNK, Bcl-2, Bax,Caspase-9,Caspase-3等蛋白的表达用Western blot检测，线粒体膜电位用JC-1染色法检测。 结果：丙戊酸钠可以显著抑制肝癌细胞的增殖并且呈现剂量-效应关系，流式细胞仪检测出现了明显的亚二倍体峰和凋亡细胞群，hoechest 33258染色来检测出现了明显的核固缩、边聚和裂解。JC-1染色法显示线粒体膜电位发生了明显的改变，JNK, p-JNK, Bcl-2, Bax,Caspase-9,Caspase-3等蛋白的表达也发生了改变。 结论：丙戊酸钠通过线粒体凋亡通路诱导肝癌细胞凋亡。

Sodium Valproate induces mitochondria-dependent apoptosis in human Hepatocellular carcinomar cells

Background: several research groups have reported that Sodium Valproate can inhibite the proliferation of cancer cells in neuroblastoma, glioma and so on. the effect of Sodium Valproate on the proliferation and apoptosis of Hepatocellular carcinomar cells has been discovered in recent years. but the molecular mechanisms of its antitumor effect is little known.To evaluate the effects of Sodium Valproate on the proliferation and apoptosis of HepG2 cells. To explore the mechanism of Sodium Valproate inducing apoptosis in human Hepatocellular carcinomar cells. Methods: The effects of Sodium Valproate on the proliferation of HepG2 cells were evaluated by WST assay and clone formation assay. The morphological changes were detected by fluorescence microscopy assay. DNA ploidy and apoptotic cell percentage were calculated by the flow cytometry. The expression of JNK, p-JNK, Bcl-2, Bax,Caspase-9,Caspase-3 was analyzed by Western blot. The membrane potential of mitochondria was detected by JC-1 fluorescence microscopy assay. Results: Our results demonstrated Sodium Valproate could inhibit the proliferation of HepG2 cells via induction of apoptosis, with the evidence of characteristic morphologic changes of apoptosis in the nucleus, Furthermore, DNA ploidy analysis showed that the percentage of hypodiploid cells was accumulated in a dose-dependent manner. The membrane potential of mitochondria was changed. The protein levels of JNK, Bcl-2, Bax, pro-Caspase-9, pro-Caspase-3 were changed after treated with Sodium Valproate., Treatment of cancer cells with Sodium Valproate increased the phosphorylation of JNK. Conclusion: Sodium Valproate can inhibit the proliferation and trigger mitochondria-dependent apoptosis in HepG2 cells.