牡蛎天然活性肽对人胃腺癌BGC-823细胞周期与基因表达的调控

Regulation of bioactive peptides of oyster(BPO)on the cell cycle and gene expression of human gastric adenocarcinoma cell-line BGC-823

目的比较研究牡蛎天然活性肽(BPO)对人胃腺癌BGC-823细胞凋亡的生物学效应,并进一步探索其对胃癌细胞的作用机制。方法采用酸抽提、凝胶柱层析等方法,从牡蛎体内分离提取到牡蛎天然活性多肽组分BPO-1,以姜黄素和HMBA处理组为平行对照,流式细胞仪检测细胞周期变化及以免疫细胞化学方法检测相关癌基因、抑癌基因表达变化。结果BPO-1能有效抑制BGC-823细胞增殖活动,出现亚G1期细胞,细胞进入凋亡现象。BPO-1,姜黄素及其组合均能不同程度地上调BGC-823细胞p16,c-myc,Fas,p21WAF1/CIP1蛋白表达,下调突变型p53,bcl-2蛋白表达。结论BPO-1对胃癌细胞具有显著的诱导凋亡作用。其诱导癌细胞凋亡机制与其调节和干预bcl-2,c-myc等癌基因和p53,p16,p21WAF1/CIP1等抑癌基因的表达有关。

Objective To investigate the effects and mechanism of bioactive peptides of oyster （BPO）on the apoptosis of human gastric adenocarcinoma cell line BGC-823. Methods BPO-1, isolated from Ostrea cucullata by acid extraction and gel chromatography, was used to treat the BGC-823 cells. Curcumin and HMBA were used as control. Cell-cycle was detected by flow cytometer, some oncogene and tumor repressive gene were detected by lmmunocytochemistry analysis. Results BPO-1 could effectively inhibit the proliferation of BGC -823 cells,induce cells into sub-G1 phase. BPO-l,curcumin and their combination could up- regulate the expression of gene p16, c-myc, Fas, p21^WAF1/CIP1 , and down-regulate gene p53, bcl-2. Conclusion BPO-1 could effectively induce BGC-823 cells into apoptosis, and the apoptosis effect involved to the changes of oncogene and tumor repressive gene.