倍半萜化合物Chabranol诱导低分化胃癌细胞凋亡的分子机制

Molecular mechanism of apoptosis in poorly differentiated gastric cancer cells induced by Chabranol

目的探讨倍半萜化合物Chabranol诱导低分化胃癌细胞BGC-823发生凋亡可能的分子机制。方法采用透射电镜观察凋亡细胞超微结构的变化;实时荧光定量PCR法检测Chabranol处理前后各组细胞中凋亡相关基因p53、Bcl-2、Bax、Survivin、Caspase-3的转录表达水平。结果在高倍透射电镜下,Chabranol处理组BGC-823细胞出现早期凋亡现象,细胞核中异染色质明显增多,髓样体增多,而对照组BGC-823细胞结构完整。实时荧光定量PCR结果显示:与对照组比较,Chabranol处理后的BGC-823细胞p53、Bcl-2和Survivin降低,Bax和Caspase-3增加,均P<0.05,差异有统计学意义;GES-1、MKN28、SGC-7901细胞各基因的相对表达量与对照组比较,P>0.05,差异无统计学意义。结论倍半萜化合物Chabranol具有潜在的抗胃癌活性,有可能成为治疗低分化胃癌的新药物,其致低分化胃癌细胞凋亡的分子机制与p53、Bcl-2、Bax、Survivin、Caspase-3基因的异常转录表达相关。

Objective To investigate the possibility molecular mechanism of apoptosis induced by Chabranol in poorly differentiated gastric cancer cells. Methods The ultrastructural changes of apoptotic cells were observed by transmission electron microscopy. The expression of p53, Bcl-2, Bax, Survivin and Caspase-3 genes were detected by real-time fluorescence quantitative PCR before and after treatment. Results Under the high TEM, the apoptotic cells appeared in the drug group, the heterochromatin in the nucleus was increased, the myeloid was increased and the cell structure in the control group was intact. The results of fluorescence quantitative PCR showed that the relative expression of p53, Bcl-2, Bax, Survivin and Caspase-3 were respectively decreased, decreased, increased and decreased in BGC-823 cells treated by Chabranol（P〈0.05）, while the relative expression of each gene in GES-1, MKN28 and SGC-7901 cells remained unchanged（P〉0.05）.Conlusion The Chabranol has potential anti-gastric cancer activity and may become a new drug for the treatment of poorly differentiated gastric cancer. The molecular mechanism of apoptosis induced by Chabranol in poorly differentiated gastric cancer cells is associated with p53, Bcl-2, Bax, Survivin and Caspase-3 gene＇s expression.