Abstract: AIM: To investigate the anti-colon cancer effects of rosiglitazone and possible relationship with COX-2. METHODS: Wistar rat colon cancer model was induced by 1-2 dimethylhydrazine (DMH)(40 mg/kg s.c.)+1% dextran sodium sulfate solution (DSS)(freely drinking). All rats were randomly divided into 3 groups:control(DMH + DSS + solvant), rosiglitazone(Ros) (DMH+DSS+Ros 0.75 mg·kg^-1·d^-1) , meloxicam(Mel):(DMH+DSS+Mel 1.35 mg·kg^-1·d^-1). The drugs were given orally once a day for 5 day per week. The body weight, the number of colon ACFs, the incidence and number of colon cancer in rats, as well as the morphological changes of rat colon tissues were evaluated. Human colon cancer Lovo cell line was treated by either Ros or Mel in various concentrations (10^-6,10^-5,10^-4,10^-3 mol/ L) for 6 h,12 h and 24 h,respectively, and the cell growth was assayed by MTT method. Western blot were used to evaluate the protein expressions of COX-2 from Lovo cells treated with Ros.RESULTS: Ros significantly improved the dyscrasia induced by DMH+DSS, the both of body weight and general condition were better than those of control group. Ros also significantly inhibited ACF and colon cancer incidence in the rats treated by DMH+DSS for 10 weeks or 20 weeks,which was similar to that of Mel. Ros inhibited the proliferation of Lovo cells in concentration- and time-dependent manners, and the IC₅₀ values were significantly smaller than that of Mel at 6 h,12 h, and 24 h after Lovo cells were treated by either Ros or Mel. Ros also concentration-dependently decreased expressions of COX-2 protein.CONCLUSION: Ros can inhibit ACF and tumor formation induced by DMH+DSS,and decrease the Lovo cell proliferation index. The anti-tumor effects of Ros may involve in an unknown pathway through which the expressions of COX-2 were inhibited.

Key words: Rosiglitazone, Colon cancer, COX-2, Chemoprevention