Mechanism of inhibition on activator protein-1 activity by all-trans retinoic acid in gastric cancer cells

OBJECTIVE: To determine the mechanism of all-trans retinoic acid (ATRA) on growth inhibition in human gastric cancer cells. METHODS: Gastric cancer cell lines: MGC80-3, BGC-823, SGC-7901 and MKN-45. CAT assay, Northern blot, Western blot, gene transfection and MTT assay. RESULTS: ATRA can inhibit the activator protein-1 (AP-1) activity in ATRA-sensitive cell lines, but not in ATRA-resistant cell line, and the anti-AP-1 activity of ATRA is mediated by its receptor, retinoic acid receptor alpha (RAR alpha). ATRA can also inhibit the expression of cJun and cFos. One of the mechanisms for ATRA to inhibit the growth of gastric cancer cells may be through its inhibitory effect on the AP-1 activity and its influence on up-regulation of RAR alpha expression. The inhibition of cJun and cFos expressions by ATRA may also contribute to the anti-AP-1 activity. CONCLUSIONS: ATRA inhibits the growth of gastric cancer cells through the regulation of AP-1 activity. This action is mediated by RAR alpha.