Abstract:

 Objective   To explore rosiglitazone-induced sensitization of LOVO cells to 5-Fu. Methods   In vivo studies: A heterotopic xenograft model in athymic mice using LOVO human colon cancer cell was established, and the animals were treated with rosiglitazone and/or 5-Fu through intragastric administration for two weeks. The tumors were measured for length and width every other day, and  tumor volumes and inhibiting rates were calculated. In vitro studies: The anti-proliferation effect of rosiglitazone in conjunction with 5-Fu to LOVO cells was measured  using the MTT assay. The morphology of nuclei was observed after staining with Hoechst 33342. Cell cycle distribution was detected using flow cytometry after propidium iodide staining. The expression of Cyclin A1, Cyclin E1 and Cdk2 was detected by Western blotting analysis. Results   In vivo studies: The tumor-inhibiting rates of rosiglitazone, 5-Fu, and rosiglitazone plus 5-Fu were 67.97%, 74.9% and 80.49%, respectively. The two drugs were found to have an additive effect. In vitro studies: Rosiglitazone sensitizes 5-Fu′s growth inhibition to LOVO cells in a dose- and timedependent manner. Cell numbers of S phase were increased by 10μmol/L 5-Fu plus rosiglitazone. The 5-Fu group showed Cyclin A1 down-regulation relative to the Control group, and the 5-Fu/rosiglitazone group showed further Cyclin A1 down-regulation. Compared to the Control group, all the drug groups exhibited down-regulation of Cyclin E1 and Cdk2, and the 5-Fu/rosiglitazone group exhibited further Cyclin E1 down-regulation. Conclusion   Rosiglitazone enhances 5-Fu-induced LOVO cell growth inhibition through S cycle arresting.

Key words: Peroxisome proliferator-actived recepter gamma; Rosiglitazone; 5-Fluorouracil; Nude mice; LOVO cells; S phase cycle arrest