Antitumor effect and it’s mechanism of tranilast in gastric cancer cell lines *
An antitumor effect of tranilast was examined in five gastric cancer cell lines. Tranilast showed a dose-dependent antitumor effect in all of these gastric cancer cell lines with IC50 at80－240μM. In combination with typical anticancer drugs, including cisplatin（CDDP）, 5-fluorouracil, and paclitaxel, tranilast had a synergistic effect on the anti-proliferative activity of these anticancer drugs. From cell cycle analysis, a dose-dependent increase in G0-G1 phase was noted with tranilast alone, and an increase in the subG1 phase which resulted in an increased proportion of apoptotic cells, was observed after tranilast and CDDP treatment as compared with CDDP alone. Immunohistochemical staining showed nuclear expansion and fragmentation with tranilast. Enhancement of p53 and p21 expression was detected six hours after the addition of tranilast with Western blot analysis. These results suggest that tranilast inhibits the proliferation of gastric cancer cells through G1 arrest associated with the induction of p21 and p53, and that it has a synergistic effect on the anti-proliferative activity of antitumor drugs. (Accepted on October 15，2007)
