棉酚衍生物ApoG2诱导胃癌细胞凋亡及对Wnt6调控作用的研究

ApoG2 induces apoptosis of gastric carcinoma cells and suppresses Wnt 6 expression

目的研究棉酚衍生物ApoG2诱导胃癌细胞凋亡作用及对Wnt6调控作用的影响。方法以人胃腺癌细胞系BGC823细胞为模型,检测ApoG2作用下BGC823细胞生长抑制、形态学变化和细胞周期变化,以及给药前、后细胞Bcl2、Bax和Bak mRNA表达水平和Wnt6蛋白表达水平的变化。结果 ApoG2对BGC823细胞的生长抑制呈浓度依赖性,给药后经Hoechst染色可观察到典型凋亡细胞,经PI染色用流式细胞仪可检测到明显sub-G1峰;Wnt6蛋白含量和Bcl2 mRNA含量随ApoG2浓度升高而降低,Bax和Bak mRNA含量随ApoG2浓度升高而升高。结论 ApoG2能明显抑制人胃癌细胞BGC823的生长,诱导细胞凋亡,可能通过抑制细胞Wnt6蛋白表达从而调控Bcl2蛋白家族的基因转录,继而引起细胞凋亡。

Objective To investigate the apoptosis-inducing effect of ApoG2 on gastric carcinoma ceils and its influence on Wnt6 expression. Methods Experiments were performed on human gastric carcinoma cell line BGC823. Cell viability, cell morphology and cell cycle were detected after ApoG2 treatment. The mRNA Levels of Bcl2, Bax, Bak and Wnt6 protein were also examined. Results BGC823 cell growth was significantly inhibited by ApoG2 in a dose-dependent manner. Apoptotic cells were observed by fluorescence microscope using Hoechst staining after ApoG2 treatment. Cell cycle analysis of ApoG2 treated cells by flow cytometry displayed increased percentage of sub-G1 peak. Increased mRNA levels of Bax and Bak after ApoG2 treatment were observed, while both Bcl2 mRNA level and Wnt6 protein level were decreased. Conclusions ApoG2 can significantly inhibit the growth of human gastric carcinoma BGC823 cells and induce cell apoptosis. This effect is probably mediated by the suppression of Wnt6 protein which downregulates Bcl2 gene expression and upregnlates Bax and Bak gene expression.