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 (2011)

You have accessJournal of UrologyKidney Cancer: Basic Research1 Apr 2011244 ARE ALL MULTI-TARGETED TYROSINE KINASE INHIBITORS CREATED EQUAL? DISPARATE IN VITRO ACTIVITY OF PAZOPANIB AND SUNITINIB AGAINST HUMAN RENAL CELL CARCINOMA CELL LINES Daniel Canter, Alexander Kutikov, Konstantin Golovine, Petr Makhov, Robert G. Uzzo, and Vladimir M. Kolenko Daniel CanterDaniel Canter Philadelphia, PA More articles by this author , Alexander KutikovAlexander Kutikov Philadelphia, PA More articles by this author , Konstantin GolovineKonstantin Golovine Philadelphia, PA More articles by this author , Petr MakhovPetr Makhov Philadelphia, PA More articles by this author , Robert G. UzzoRobert G. Uzzo Philadelphia, PA More articles by this author , and Vladimir M. KolenkoVladimir M. Kolenko Philadelphia, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.313AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail 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, HRC-24, 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 CellTiter-Blue 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. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e99 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel Canter Philadelphia, PA More articles by this author Alexander Kutikov Philadelphia, PA More articles by this author Konstantin Golovine Philadelphia, PA More articles by this author Petr Makhov Philadelphia, PA More articles by this author Robert G. Uzzo Philadelphia, PA More articles by this author Vladimir M. Kolenko Philadelphia, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...