title: Are all multi-targeted tyrosine kinase inhibitors created equal? An in vitro study of sunitinib and pazopanib in renal cell carcinoma cell lines.
abstract: OBJECTIVE
  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, SK-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) for inhibition of cellular proliferation or induction of apoptosis were calculated for sunitinib and pazopanib in each RCC cell line.
  
  
  RESULTS
  Both sunitinib and pazopanib exhibited anti-proliferative activity to varying degree 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 failed to induce apoptosis in any of the examined human RCC cell lines even at maximal concentrations.
  
  
  CONCLUSIONS
  Although sunitinib and pazopanib are often used interchangeably in the clinical setting, our results suggest that in-vitro biological activity of the two agents differs. Sunitinib exhibits a cytotoxic effect on RCC cell lines, while pazopanib's activity is solely cytostatic. These data may be clinically relevant given the current lack of comparative in-vivo studies between the two agents.
authors.affiliation: Division of Urologic Oncology, Department of Surgery, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Canter
authors.forename: Alexander
authors.initials: A
authors.lastname: Kutikov
authors.forename: Konstantin
authors.initials: K
authors.lastname: Golovine
authors.forename: Petr
authors.initials: P
authors.lastname: Makhov
authors.forename: Jay
authors.initials: J
authors.lastname: Simhan
authors.forename: Robert G
authors.initials: RG
authors.lastname: Uzzo
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Kolenko
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007191:Indazoles; D007211:Indoles / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D007191:Indazoles; D007211:Indoles; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; C516667:pazopanib; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib