Rosiglitazone Potentializing The Growth Inhibition And Apoptosis Induction Of Human Colon Cancer HT-29 Ells By Fluorouracil

Objective:To investigate the potentiation effects of rosiglitazone(ROZ) on the proliferation inhibiton and apoptosis induction of human colon cancer(HT-29)cells by fluorouracil(5-Fu) and its mechanism.Methods:Human colon cancer(HT-29) cells were cultured in vitro. HT-29 cells line were treated with various concentration of Roz or 5-Fu or both,the cell proliferation was evaluated by MTT assay. Trypan blue exclusion method was used to test the influence of growth in HT-29 cells. The apoptosis of HT-29 cells were determined by AO/EB fluorescence stain and PI staining flow cytometry. The expression of PPARy,NF-K B,Bcl-2,Bax protein were analized by Western blot.Results:5-Fu inhibited proliferation of HT-29 cells and its IC50 to HT-29 cells is 8.05?g/ml, so did Rostglitazone whose IC50 to HT-29 cells is 140. 7?mol/L. Rosiglitazone significantly increased inhibition proliferation effect of 5-Fu to HT-29 cells at 1. 0?mol/L. Trypan blue exclusion showed that rosiglitazone and 5-Fu were able to inhibit growth of HT-29 cells accompanied with increasing of concentration and time. 1.0?10.0?mol/L rosiglitazone had no cytotoxic to HT-29 cells. But Rosiglitazone at 1.?mol/L significantly increased inhibition growth effect of 5-Fu to HT-29,prolonging HT-29 cell multiple time from 50.7h to 900h,which consistent with growth curve. AO/EB fluorescence stain and PI staining flow cytometry data showed the apoptosis of HT-29 cells induced by 5-Fu and Rosiglitazone in a concentration dependent manner. Apoptosis rate of HT-29 cells treated with Rosiglitazone at 1.0?mol/L for 72h was 1.44% and treated with 5-Fu at 12. O?g/ml was 23.14%,while Rosiglitazone(1.0?mol/L) significantly promoted apoptosis induction of HT-29 cells by 5-Fu(12. O?g/ml) to 48.41%. Western blot results showed that HT-29 cells treated with ROZ reduced NF-kB?Bcl-2 proteins expression and increased Bax proteins expression via activating PPAR?protein,in a concentration dependent manner(P<0.05).Conclusion:(1)Rosiglitazone at no cytyotoxic concentration(1.0?mol/L) enhances the inhibition of proliferation and growth of human colon cancer cells by fluorouracil.(2)Rosiglitazone at nocytyotoxic concentration 1. 0?mol/L)promotes the apoptosis induction of human colon cancer cells by 5-Fu.(3)The chemosenitiaztion of Rosiglitazone to 5-Fu might be associated with downregulation expression of NF-?B, Bcl-2 protein and upregulation expression of Bax protein by activating of PPAR?.