Effects of retinoic acid on metastasis and its related proteins in gastric cancer cells in vivo and in vitro

AIM: To investigate the effects of all-trans retinoic acid (ATRA) on metastasis and its related proteins in human gastric cancer cells in vivo and in vitro. METHODS: Gastric cancer cells, MGC80-3 and SGC-7901, were inoculated into spleen subcapsule of nude mice, respectively. Nude mice were administered with ATRA (0.7 mg/kg, ig) every other day. Six weeks later, nude mice were sacrificed. All the tumors formed in spleen and in liver were removed. Some of them were fixed, and then embedded. Others were kept in liquid nitrogen for further use. Expression level of proteins in tumor and in cell was analyzed by Western blot. Microvessel in tumor section was shown by immunohistochemistry and adhesive ability of cell to amnion was measured by adhesion assay. RESULTS: When inoculated nude mice were treated with ATRA, the xenograft tumors in spleen and metastatic tumors in liver were suppressed by 50% respectively, and inhibition of microvessel formation in xenograft and metastatic tumors was also observed obviously. Although ATRA regulated expression of nm23 and mts1/p16 proteins at different patterns in vivo and in vitro, high ratio of nm23 and mts1/p16 was in association with low adhesive activity of cells. In addition, ATRA induced ICAM-1 protein expression in vivo and in vitro. CONCLUSION: ATRA inhibits the growth of xenograft tumors and their metastasis to liver. This process may be associated with regulation of metastatic related proteins, including nm23, mts1/p16, and ICAM-1 in vivo and in vitro.