Ndrg2基因表达对胃癌细胞增殖调控及其机理的研究

为研究Ndrg2基因在人类肿瘤发生发展中的作用，以不表达Ndrg2基因的胃癌细胞系HGC-27和表达Ndrg2基因的胃癌细胞系SGC-7901作为对比材料，以Ndrg2基因转染HGC-27胃癌细胞系，以及用Ndrg2的反义寡核苷酸封闭SGC-7901胃癌细胞系中Ndrg2基因的表达.发现Ndrg2可以抑制HGC-27胃癌细胞的软琼脂集落形成，有一定诱导细胞凋亡的作用，对细胞周期蛋白E的表达有明显下调作用.当封闭了SGC-7901胃癌细胞中Ndrg2基因表达的软琼脂集落形成受到抑制，流式细胞仪检测发现此时的SGC-7901细胞周期被阻滞在G1期，细胞周期蛋白D1和E表达下调.Ndrg2基因对两种肿瘤细胞中的细胞外信号调节激酶(ERK)和P38的表达也有不同的影响.

Effect of Ndrg2 Gene Expression on Gastric Carcinoma Cell Proliferation

In previous study, a PCR-based subtractive hybridization method was used to isolate the human N-myc downstream regulated gene2 (Ndrg2) located at chromosome 14q11.2. Ndrg2 is low expressed in various tumor tissues. Ndrg2 tissue expression pattern suggests that its expression level is inversely related to cell proliferation rate. To investigate tumor suppressor activity of Ndrg2 gene, it was transiently transfected to an undifferentiated gastric mucos gland carcinoma cell line HGC-27 which not expresses this gene itself confirmed by RT-PCR. It was found that the products of this gene may suppress the colony formation of gastric carcinoma cells in soft agar and induced apoptosis, as well as downregulated expression of cyclin D1 and cyclin E, but not affected cell cycle change in flowcytometry analysis. In addition, the antisense oligonucleotide of Ndrg2 gene was designed and added to the cultured differentiated gastric epidermal carcinoma cell line SGC-7901 which expressed this gene itself confirmed by RT-PCR. It was observed that the numbers of colony formation of SGC-7901 cell in soft agar decreased after Ndrg2 gene expression blocked by antisense oligonucleotide compared with sense oligonucleotide. In this case SGC-7901 cell cycle was arrested in G1 phase. These results may be related to the low expression of cyclin D1 and cyclin E in gastric carcinoma cell line SGC-7901. The results suggest that Ndrg2 gene may be of obviously key role in various differential stage gastric carcinoma cells.