基因表达谱芯片筛选奥沙利铂作用后的人结肠癌细胞凋亡基因的研究

Study on apoptosis gene of human colorectal adenocarcinoma cell lines induced by Oxaliplatin with gene expression profile

目的研究奥沙利铂作用于人结肠癌细胞系Sw1116后,诱导细胞基因表达发生差异,阐明奥沙利铂诱导肿瘤细胞凋亡的基因机制。方法用奥沙利铂(40μg/ml)处理人结肠癌细胞系Sw111612hrs,通过透射电子显微镜观察肿瘤细胞的凋亡形态学改变,通过基因表达谱芯片检测药物作用后的基因表达差异。结果经奥沙利铂作用Sw1116细胞,表现典型的凋亡形态学改变,细胞表面质膜突起消失,核固缩成团块状,染色质浓缩,沿核膜排列,线粒体基质肿胀,空泡形成,有凋亡小体形成;共有722条基因发生了差异表达,其中10条为凋亡相关基因。结论奥沙利铂通过上调某些促凋亡基因及下调某些凋亡抑制基因的表达参与调控结肠癌细胞的凋亡,证明诱导凋亡是奥沙利铂抗肿瘤作用机制之一。

Objective To investigate the molecular mechanisms of action of apoptosis of human colorectal adenocarcinoma cell line Sw1116 induced by Oxaliplatin through gene expression profile. Methods The human colorectal adenocarcinoma cell line Sw1116 was treated by Oxaliplatin(40 μg/ml) 12 hours. Morphologic changes of apoptosis were examined under transmitted electron microscope(TEM) and differentia of gene expression was detected by cDNA microarray. Results Sw1116 cells show apoptotic typical morphologic changes after administration of oxaliplatin:chromatin condensing and disposing along nuclear membrane, nucleus shrinking, apoptotic body appearing. There are total 722 differentially expressed gene, including 10 genes associated with apoptosis. Conclusion Oxaliplatin can induce the apoptosis of colorectal adenocarcinoma cell line Sw1116 through increasing the expression of some apoptosis promoting genes and decreasing the expression of some apoptosis inhibiting genes.