Sunitinib is an oral small molecular tyrosine kinase inhibitor that exhibits potent antiangiogenic and antitumor activity. Unfortunately, sunitinib kidney toxicity limits its clinical use. Renal injury caused by sunitinib treatment can not only lead to the failure of cancer treatment, but also jeopardizes the health and life of patients. Currently, there is no better intervention measure for renal injury caused by sunitinib therapy except reducing the dosage or stopping the medication. In this study, we learned from clinical case report that sunitinib can cause severe renal injury. Subsequently, we compiled the clinical trials data of sunitinib found that sunitinib can cause general renal damage. Based on this finding, we conducted a study on the mechanism of sunitinib-induced renal injury. The results showed that sunitinib can inhibit the survival of HK-2 cells (human tubule epithelial cells) in a dose- and time-dependent manner. The survival inhibition is mainly due to the activation apoptotic signaling pathway by sunitinib in HK-2 cells and induces apoptosis of HK-2 cells. Subsequently, we found that natural compound oxypeucedanin can significantly alleviate the apoptosis of HK-2 cells induced by sunitinib. Through clinical investigation and experimental study of sunitinib, we found that sunitinib can cause extensive renal damage by inducing apoptosis of renal tubular epithelial cells and natural compound oxypeucedanin is a potentially effective intervention for nephrotoxicity of sunitinib. Thus, our research will provide a theoretical basis for the future rational use of sunitinib and the search for appropriate interventions for sunitinib-induced kidney damage.
European journal of pharmacology. 2019 Oct 03 [Epub ahead of print]
Jianping Xiao, Ju Wang, Liang Yuan, Li Hao, Deguang Wang
Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, Anhui, China. Electronic address: ., Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, Anhui, China., Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, Anhui, China. Electronic address: .