2-甲基-正丁酰紫草素诱导人胃癌SGC-7901细胞凋亡机制的研究

Mechanisms of(2-methyl-n-butyl) shikonin induced apoptosis of gastric cancer SGC-7901 cells

2-甲基-正丁酰紫草素[（2-methyl-n-butyl）shikonin,MBS,图1]是从紫草科植物紫草的根部提取得到的一个萘醌类化合物。研究表明,紫草素具有抗炎、抗菌、抗肿瘤的作用[1？3]。体外实验证实紫草素通过增加caspase-3的活化诱导多种肿瘤细胞的凋亡,

This study is to investigate the effect of（2-methyl-n-butyl） shikonin（MBS） on inducing apoptosis of human gastric cancer cell line SGC-7901 and the role of ERK1/2 signal pathway in the apoptosis.MTT assay was used to detect SGC-7901 cell proliferation.DNA condensation was measured by DAPI stain.Cell apoptosis was analyzed by flow cytometry.Mitochondrial membrane potential（MMP） was analyzed by JC-1 staining.The protein expressions of Bcl-2,Bax,Survivin,cleaved caspase-9,cleaved caspase-3,cleaved PARP,p-ERK1/2,ERK1/2,p-JNK,JNK,p-p38 and p38 were detected by Western blotting.The results showed that MBS reduced the cell viability of SGC-7901 cells in a dose-and time-dependent manner.The IC50 at 24 h and 48 h for SGC-7901 cells was 10.113 and 4.196 μmol·L-1,respectively.After being treated with MBS,the typical nuclear condensation was observed in SGC-7901 cells by DAPI stain.Apoptosis in SGC-7901 cells was induced by MBS in a dose dependent manner.The protein expression of Bcl-2 was down-regulated,while the protein expressions of cleaved caspase-9,cleaved caspase-3,cleaved PARP,p-ERK1/2 and p-JNK were up-regulated after MBS treatment.U0126,a specific MAP kinase（MEK1/2） inhibitor,blocked the ERK1/2 activation by MBS.MMP was decreased by MBS treatment.It can be concluded that MBS could inhibit SGC-7901 cell proliferation and induce apoptosis.Mitochondrial apoptosis pathway,ERK1/2 signal pathway and JNK signal pathway might be involved in this process.