Overcoming sunitinib resistance with tocilizumab in renal cell carcinoma: Discordance between in vitro and in vivo effects

Sunitinib is one of the first-line multi-tyrosine kinase inhibitors for metastatic renal cell carcinoma, and resistance to sunitinib continues to be a limiting factor for the successful treatment. As interleukin-6 (IL 6) is overexpressed in sunitinib-resistant cells, the purpose of this study was to explore the potential of IL-6 inhibition with tocilizumab, an IL-6 receptor inhibitor, to overcome resistance. In vitro, two sunitinib-resistant renal cell carcinoma cell lines (Caki-1 and SN12K1) were treated with tocilizumab. A mouse subcutaneous xenograft model was also used. Cell viability was studied by MTT assay, and apoptosis by morphology and ApopTag. Expression of IL-6, vascular endothelial growth factor (VEGF), and Bcl-2 was analyzed by qPCR. In vitro, tocilizumab induced significant cell death, and reduced the expression of IL-6, VEGF, and Bcl-2 in sunitinib-resistant cells. However, the in vitro findings could not be successfully translated in vivo, as tocilizumab did not decrease the growth of the tumors. (C) 2021 Published by Elsevier Inc.

Automated summary

This study explores the potential of IL-6 inhibition with tocilizumab to overcome resistance to sunitinib in metastatic renal cell carcinoma. In vitro experiments showed that tocilizumab induced cell death and decreased the expression of IL-6, VEGF, and Bcl-2 in sunitinib-resistant cells. However, the in vivo experiments did not support these findings, as tocilizumab did not reduce tumor growth.