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

Overview

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 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.