Background/aim: Organ transplant patients treated with the immunosuppressive drug cyclosporine A often present malignant kidney tumors. Cyclosporine A can promote oncogenesis in a cell-intrinsic manner by increasing the production of vascular endothelial growth factor (VEGF).
Materials and methods: We explored the impact of cyclosporine A and the role of the unfolded protein response (UPR) on three human renal cell carcinoma (RCC) cell lines under normoxic and hypoxic (1% O2) conditions.
Results: Cyclosporine A regulated the expression of VEGF at the post-transcriptional level. Cyclosporine A induced the inositol requiring enzyme-1α (IRE1α) arm of the UPR and stabilized neosynthesized proteins in RCC cells. Toyocamycin, an inhibitor of IRE1α, abolished the clonogenic growth of RCC cells and reduced induction of VEGF by cyclosporine A under hypoxia.
Conclusion: Our findings highlight the impact of cyclosporine A on the proteostasis of RCC cells, and suggest the potential therapeutic interest of targeting the UPR against tumors arising in the context of organ transplantation.
Keywords: Cyclosporine A; renal cell carcinoma; toyocamycin; unfolded protein response; vascular endothelial growth factor.
Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.