摘要目的探讨ATRA调节胃癌细胞生长的作用机理.方法 Western blot测定蛋白表达水平,免疫沉淀测定蛋白激酶活性,MTT方法检测细胞生长和流式细胞术分析细胞周期.结果 ATRA有效地诱导细胞滞留G0/G1期并抑制胃癌细胞生长.ATRA通过依赖P53和非依赖P53途径诱导ATRA敏感细胞的P21WAF1/CIP1表达,由此导致CDK4和CDK2活性下降,但对CDK4和CDK2蛋白表达没有影响.另外,由于ATRA抑制CDK4和CDK2活性,导致Rb蛋白去磷酸化水平上升.结论 ATRA通过调节细胞周期进程的相关蛋白而抑制胃癌细胞生长.

abstractsObjective　To investigate the mechanism of all-trans retinoic acid (ATRA) on the regulation of the cell cycle in gastric cancer cells. Methods　The protein level was detected by Western blot. Immunoprecipitation was used in protein kinase activity determination. Cell growth and cell cycle phase were examined by MTT assay and flow-cytometric analysis, respectively.Results　ATRA could effectively induce G0/G1 arrest and inhibit cell growth in certain human gastric cancer cell lines. ATRA might induce p21WAF1/CIP1 expression in ATRA-sensitive cell lines through p53-dependent and p53-independent pathways. Induction of p21WAF1/CIP1 caused decrease in CDK4 and CDK2 activities independent of CDK4 and CDK2 protein expression levels. In addition, the dephosphorylated form of Rb protein increased because of the down-regulation of CDK4 and CDK2 activities by ATRA. Conclusions　Growth inhibition on gastric cancer cells by ATRA occurs through the regulation of relevant proteins leading to the arrest of cell cycle progression.