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Are all multi-targeted tyrosine kinase inhibitors created equal? An in vitro study of sunitinib and pazopanib in renal cell carcinoma cell lines
Division of Urologic Oncology, Department of Surgery, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
Address correspondence to Dr. Alexander Kutikov, Department of Surgical Oncology, Division of Urology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia PA19111 USA
Canadian Journal of Urology 2011, 18(4), 5819-5825.
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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 cell 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 both sunitinib and pazopanib in each RCC cell line.
Results: Both sunitinib and pazopanib exhibited anti-proliferative activity to varying degrees against all human RCC cell lines; however, sunitinib achieved its effects 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 RCC cell lines, even at maximal concentrations.
Conclusions: Although sunitinib and pazopanib are often used interchangeably in clinical practice, our results suggest that their in vitro biological activities differ. Sunitinib exhibits a cytotoxic effect on RCC cell lines, while pazopanib’s activity is solely cytostatic. These findings may have clinical relevance, particularly in the absence of comparative in vivo studies between the two agents.
Keywords
advanced kidney cancer, tyrosine kinase inhibitors, pazopanib, sunitinib
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APA Style
Canter, D., Kutikov, A., Golovine, K., Makhov, P., Simhan, J. et al. (2011). Are all multi-targeted tyrosine kinase inhibitors created equal? An in vitro study of sunitinib and pazopanib in renal cell carcinoma cell lines. Canadian Journal of Urology, 18(4), 5819–5825.
Vancouver Style
Canter D, Kutikov A, Golovine K, Makhov P, Simhan J, Uzzo RG, et al. Are all multi-targeted tyrosine kinase inhibitors created equal? An in vitro study of sunitinib and pazopanib in renal cell carcinoma cell lines. Can J Urology. 2011;18(4):5819–5825.
IEEE Style
D. Canter et al., “Are all multi-targeted tyrosine kinase inhibitors created equal? An in vitro study of sunitinib and pazopanib in renal cell carcinoma cell lines,” Can. J. Urology, vol. 18, no. 4, pp. 5819–5825, 2011.
Copyright © 2011 The Author(s). Published by Tech Science Press.This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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