Human urothelial carcinoma cell response to Sunitinib malate therapy in vitro.

OBJECTIVES

Bladder transitional cell carcinoma (TCC) is one of the most common solid malignancies in China. This study examined the antitumor effect and underlying mechanism of action of sunitinib malate in human bladder TCC in vitro.

METHODS

Bladder TCC cell lines 5637 and BIU87 were maintained in 1640 medium and T24 cell lines in DMEM/F12 medium. All 3 cell lines were then exposed to graded concentrations (0.625-20 μmol/L) of sunitinib malate, sorafenib and cisplatin for 24-96 hours to determine the sensitivities to each drug. Cell viability was measured by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium] assay, and apoptosis was analyzed by flow cytometry. Cell apoptotic morphology was observed by a fluorescence microscope after DAPI (4',6-diamidino-2-phenylindole) staining. Protein concentrations were measured by western blot.

RESULTS

Sunitinib malate showed a concentration-dependent inhibitory effect on the 5637, T24 and BIU87 cell lines with IC50's of 1.74 μmol/L, 4.22 μmol/L, and 3.65 μmol/L, respectively. Cisplatin also exhibited good antitumor activity, but whereas sorafenib suppressed proliferation of the cells at concentrations of 10 μmol/L or higher, there was practically no response at lower concentrations. Sunitinib malate treatment resulted in an accumulation of cells in the sub-G1 phase, especially with the T24 and BIU87 cell lines, which induced apoptosis of the cells.

CONCLUSIONS

Sunitinib malate exerted marked inhibitory activity against bladder cancer cells. The cell growth inhibitory effect of the drug was related to induction of apoptosis. These results suggest that clinical application of sunitinib-based therapy for advanced bladder cancer is possible.