Losartan Alleviates the Side Effects and Maintains the Anticancer Activity of Axitinib
Ying Fu,
Rengui Saxu,
Kadir Ahmad Ridwan,
Jiaping Yao,
Xiaoxuan Chen,
Xueping Xu,
Weida Zheng,
Peng Yu,
Yuou Teng
Affiliations
Ying Fu
China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Bioengineering, Tianjin University of Science and Technology, Tianjin 300457, China
Rengui Saxu
China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Bioengineering, Tianjin University of Science and Technology, Tianjin 300457, China
Kadir Ahmad Ridwan
China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Bioengineering, Tianjin University of Science and Technology, Tianjin 300457, China
Jiaping Yao
China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Bioengineering, Tianjin University of Science and Technology, Tianjin 300457, China
Xiaoxuan Chen
China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Bioengineering, Tianjin University of Science and Technology, Tianjin 300457, China
Xueping Xu
China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Bioengineering, Tianjin University of Science and Technology, Tianjin 300457, China
Weida Zheng
Medical College, Yanbian University, No. 977 Gongyuan Road, Yanji 133002, China
Peng Yu
China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Bioengineering, Tianjin University of Science and Technology, Tianjin 300457, China
Yuou Teng
China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Bioengineering, Tianjin University of Science and Technology, Tianjin 300457, China
Axitinib is one of the most potent inhibitors of the vascular endothelial growth factor (VEGF) receptor and shows strong antitumor activity toward various malignant tumors. However, its severe side effects affect the quality of life and prognosis of patients. Losartan, which functions as a typical angiotensin receptor blocker, controls the average arterial pressure of patients with essential hypertension and protects against hypertension-related secondary diseases, including proteinuria and cardiovascular injury. To explore the effects of losartan on side effects caused by axitinib and its antitumor activity, several animal experiments were conducted. This study first analyzed and explored the effect of losartan on the amelioration of side effects in Wistar rats caused by axitinib. The results showed that the systolic blood pressure of Wistar rats was significantly increased by about 30 mmHg in 7 days of axitinib treatment, while the combination of losartan significantly reduced the blood pressure rise caused by axitinib. The Miles experimental model and mouse xenograft tumor model were further used to evaluate the effect of losartan on the antitumor effect of axitinib. The result clearly demonstrated that losartan has no significant influence on axitinib-related low vascular permeability and antitumor activity. In summary, our results showed that the combination of axitinib and losartan significantly reduced the side effects and maintained the antitumor effects of axitinib. This study provides information for overcoming VEGF receptor inhibitor-related side effects.
