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 u...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.展开更多
基金ThisworkwassupportedbytheNationalOutstandingYouthScienceFoundationofChina (Btype No 3982 5 5 0 2 )theNationalNaturalScienceFoundationofChina (No .39880 0 15 )
文摘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.
