ORIGINAL ARTICLE Inhibition of b-catenin and STAT3 with a curcumin analog suppresses gastric carcinogenesis in vivo

Background Potent chemotherapy for advanced gastric cancer has not been completely established. Many molec-ularly targeted therapies are under investigation, but their therapeutic outcomes are not promising because they do not target specific and/or critical targets of gastric carci-nogenesis. Although the molecular basis of gastric carci-nogenesis remains poorly understood, nuclear localization of b-catenin was observed in approximately 50 % of gas-tric cancer specimens. Recent studies have suggested that activation of signal transducer and activator of transcrip-tion 3 (STAT3) contributes to gastric carcinogenesis in a mouse model. A newly synthesized curcumin analog has inhibitory potential against b-catenin and STAT3. Methods Using a transgenic mouse model of gastric cancer in which b-catenin, cyclooxygenase 2, and micro-somal prostaglandin E synthase 1 activation is induced, we examined a curcumin analog with the most enhanced potential for treating gastric cancer through oral adminis-tration. Inhibition of these targets was demonstrated using microarray and immunohistochemical analyses. Results The curcumin analog GO-Y031 decreased the incidence of gastric carcinogenesis to 54.5 % of that of the control (50.0 % vs 91.7 %, p = 0.043), and tumor size was reduced to 51.6 % of that of the control (1.6 mm vs 3.1 mm, p = 0.03). b-Catenin and STAT3 levels were suppressed to 26.2 % (p = 0.00023) and 44.8 % (p = 0.025), respectively, of those of the control. More-over, macrophage infiltration was suppressed with GO-Y031. Conclusion b-Catenin and STAT3 can be pharmacolog-ically inhibited in vivo with a curcumin analog, which effectively inhibits b-catenin and STAT3