Growth inhibition of gastric cancer cells by all-trans retinoic acid through arresting cell cycle progression

Objective 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 cy cle phase were examined by MTT assay and flow-cytometric analysis, respecti vely. Results ATRA could effectively induce G(0)/G(1) arrest and inhibit cell gro wth in certain human gastric cancer cell lines. ATRA might induce p21(WAF1/ CIP1) expression in ATRA-sensitive cell lines through p53-dependent and p53 -independent pathways. Induction of p21(WAF/CIP1) caused decrease in CDK4 a nd CDK2 activities independent of CDK4 and CDK2 protein expression levels. In addition, the dephosphorylated form of Rb protein increased because of t he down-regulation of CDK4 and CDK2 activities by ATRA. Conclusions Growth inhibition on gastric cancer cells by ATRA occurs throug h the regulation of relevant proteins leading to the arrest of cell cycle p rogression.