TY - JOUR
T1 - Are all multi-targeted tyrosine kinase inhibitors created equal? An in vitro study of sunitinib and pazopanib in renal cell carcinoma cell lines
AU - Canter, Daniel
AU - Kutikov, Alexander
AU - Golovine, Konstantin
AU - Makhov, Petr
AU - Simhan, Jay
AU - Uzzo, Robert G.
AU - Kolenko, Vladimir M.
PY - 2011/8
Y1 - 2011/8
N2 - 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, 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.
AB - 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, 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.
KW - Advanced kidney cancer
KW - Pazopanib
KW - Sunitinib
KW - Tyrosine kinase inhibitors
UR - http://www.scopus.com/inward/record.url?scp=84856011460&partnerID=8YFLogxK
M3 - Article
SN - 1195-9479
VL - 18
SP - 5819
EP - 5825
JO - Canadian Journal of Urology
JF - Canadian Journal of Urology
IS - 4
ER -