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.