244 ARE ALL MULTI-TARGETED TYROSINE KINASE INHIBITORS CREATED EQUAL? DISPARATE IN VITRO ACTIVITY OF PAZOPANIB AND SUNITINIB AGAINST HUMAN RENAL CELL CARCINOMA CELL LINES

Abstract

INTRODUCTION AND OBJECTIVES: We examined the in vitro cellular effects of the multi-targeted receptor tyrosine kinase inhibitors (TKIs) sunitinib and pazopanib on a series of human renal cell carcinoma (RCC) cell lines. METHODS: The human RCC cell lines 769-P, 786-O, HRC24, HRC-31, HRC-45, HRC-78, RCC-26B, and SK-45 were treated with varying concentrations of sunitinib and pazopanib. Cellular proliferation and cellular death were assessed using the CellTiterBlue Cell Viability Assay and the TUNEL assay, respectively. Effective doses (ED) were calculated to compare the effective concentrations at which cellular proliferation was inhibited or apoptosis was induced between sunitinib and pazopanib. RESULTS: Both sunitinib and pazopanib exhibited anti-proliferative activity to varying degrees against all human RCC cell lines; however, sunitinib’s effects were achieved at significantly lower concentrations. Moreover, sunitinib had a direct pro-apoptotic effect on all tested cell lines while pazopanib did not induce apoptosis in any of the examined human RCC cell lines even at the highest tested concentrations. CONCLUSIONS: Although sunitinib and pazopanib are used interchangeably in the clinical setting, our results suggest that sunitinib might exhibits a direct cytotoxic effect on human RCC cells, whereas the action of pazopanib is limited to cytostasis. Further studies are warranted in order to ascertain the in vivo significance of these findings.