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目的 研究全反式维甲酸 (retinoicacid ,RA)RA5 38诱导胃癌细胞的凋亡作用及其分子机制。方法 采用MTT、DNA梯度降解试验、原位末端标记、RT PCR、Westernblot等方法 ,对RA5 38重组腺病毒 (Ad)在人胃癌细胞系中生物学作用及其分子机制进行体内外研究。结果 Ad RA5 38对SGC790 1细胞能产生明显的生长抑制效应 ,诱导SGC790 1细胞凋亡。Ad RA5 38生长抑制率为 76 3%。Ad RA5 38对SGC790 1细胞产生的抑瘤效应及诱导凋亡作用是c myc、bcl 2、bax、cyclinD1等一系列基因表达变化及其相互作用的结果 ,其中对c myc及bax表达的调节作用是在RNA和蛋白水平。而对p5 3、p16、TGase、ras基因的表达没有明显影响。经Ad RA5 38处理的SGC790 1细胞致瘤性消失。Ad RA5 38对裸鼠皮下移植瘤模型瘤内注射能有效降低肿瘤的生长速度 ,生长抑制率为 6 0 7%。结论 Ad RA5 38对胃癌细胞具有显著的生长抑制及凋亡诱导作用。其作用可能与抑制c myc、bcl 2、cyclinD1基因及刺激bax基因表达的机制相关。与p5 3、p16、TGase及ras基因的表达无明显关系。
Objective To study the apoptosis and its molecular mechanism of all-trans retinoic acid (RA) RA5 38 induced gastric cancer cells. Methods The biological effects and molecular mechanisms of RA5 38 recombinant adenovirus (Ad) in human gastric cancer cell lines were studied in vitro and in vivo using MTT assay, DNA gradient assay, in situ end labeling, RT PCR, and Western blot. Results Ad RA5 38 could significantly inhibit the growth of SGC790 1 cells and induce apoptosis of SGC790 1 cells. The inhibition rate of Ad RA5 38 growth was 76 3%. The anti-tumor and apoptosis-inducing effects of Ad RA5 38 on SGC790 1 cells are the results of a series of gene expression changes and interactions of c myc, bcl 2, bax, cyclin D1, etc., and the regulation of c myc and bax expression. It is at the RNA and protein level. However, there was no significant effect on the expression of p53, p16, TGase and ras genes. The tumorigenicity of SGC790 1 cells treated with Ad RA5 38 disappeared. The intratumoral injection of Ad RA5 38 in the subcutaneous xenograft model of nude mice can effectively reduce the growth rate of the tumor, and the growth inhibition rate was 60.7%. Conclusion Ad RA5 38 has significant growth inhibition and apoptosis-inducing effects on gastric cancer cells. Its role may be related to the mechanism of inhibition of c myc, bcl 2 , cyclinD1 gene and stimulation of bax gene expression. There was no significant relationship between the expression of p53, p16, TGase and ras genes.