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.
Medical College, Yanbian University, No. 977 Gongyuan Road, Yanji 133002, China.
Molecules. 2022 Apr 26;27(9):2764. doi: 10.3390/molecules27092764.
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.
阿昔替尼是血管内皮生长因子（VEGF）受体的最有效抑制剂之一，对各种恶性肿瘤显示出强烈的抗肿瘤活性。然而，其严重的副作用会影响患者的生活质量和预后。氯沙坦是一种典型的血管紧张素受体阻滞剂，可控制原发性高血压患者的平均动脉压，并预防与高血压相关的继发性疾病，包括蛋白尿和心血管损伤。为了探索氯沙坦对阿昔替尼引起的副作用和抗肿瘤活性的影响，进行了几项动物实验。本研究首先分析和探讨了氯沙坦对阿昔替尼引起的 Wistar 大鼠副作用改善的作用。结果表明，在阿昔替尼治疗的 7 天内，Wistar 大鼠的收缩压显著升高约 30mmHg，而氯沙坦的联合使用则显著降低了阿昔替尼引起的血压升高。进一步使用 Miles 实验模型和小鼠异种移植肿瘤模型评估了氯沙坦对阿昔替尼抗肿瘤作用的影响。结果清楚地表明，氯沙坦对阿昔替尼相关的低血管通透性和抗肿瘤活性没有显著影响。综上所述，我们的结果表明，阿昔替尼和氯沙坦的联合使用显著降低了副作用，并维持了阿昔替尼的抗肿瘤作用。这项研究为克服 VEGF 受体抑制剂相关副作用提供了信息。
