Olmesartan Potentiates the Anti-Angiogenic Effect of Sorafenib in Mice Bearing Ehrlich's Ascites Carcinoma: Role of Angiotensin (1–7)

Abstract

Local renin-angiotensin systems exist in various malignant tumor tissues; this suggests that the main effector peptide, angiotensin II, could act as a key factor in tumor growth. The underlying mechanisms for the anti-angiogenic effect of angiotensin II type 1 receptor blockers need to be further evaluated. The present study was carried out to investigate the anti-angiogenic effect of olmesartan alone or in combination with sorafenib, an angiotensin (1–7) agonist or an angiotensin (1–7) antagonist in Ehrlich's ascites carcinoma-bearing mice. The tumor was induced by intradermal injection of Ehrlich's ascites carcinoma cells into mice. Tumor discs were used to evaluate the microvessel density; the serum levels of vascular endothelial growth factor (VEGF) and serum insulin-like growth factor I (IGF-I); and their intratumoral receptors, VEGF receptor-2 and IGF-I receptor, respectively. All parameters were determined following the treatment course, which lasted for 21 days post-inoculation. Monotherapy with olmesartan and its combination with sorafenib resulted in a significant reduction in microvessel density and serum levels of VEGF and IGF-I, as well as their intratumoral receptors. In addition, the combination of olmesartan (30 mg/kg) with an angiotensin (1–7) agonist reduced the microvessel density, IGF-I serum levels and the levels of its intratumoral receptor. In conclusion, olmesartan reduced the levels of the angiogenesis markers IGF-I and VEGF and down-regulated the intratumoral expression of their receptors in a dose-dependent manner, and these effects were dependent on the angiotensin (1–7) receptor. These results suggest that olmesartan is a promising adjuvant to sorafenib in the treatment of cancer.

Antitumor activity of methoxylated flavonoids separated from Achillea fragrantissima extract in Ehrlich’s ascites carcinoma model in mice

“…Ehrlich's ascites carcinoma (EAC) is referred to as an undifferentiated carcinoma which resembles tumors appearing in human and is widely used in many studies as a model to evaluate and determine the antitumor effect of natural compounds (10,11). EAC cell line was purchased from National Cancer Institute, Cairo University, Cairo in Egypt.…”

Design and Synthesis of Pyridazine Containing Compounds with Promising Anticancer Activity

“…The Research Ethics Committee at the Faculty of Pharmacy, Suez Canal University (license number 20148A2), approved the study of protocol. EAC is commonly employed as a solid form 18,19) and easy to grow in suspension, when injected in the peritoneal cavity of female mice. Mice carrying EAC cell line were obtained from the Department of Tumor Biology at the National Cancer Institute (Cairo, Egypt).…”

Synthesis of New <i>N</i>¹-Substituted-5-aryl-3-(3,4,5-trimethoxyphenyl)-2-pyrazoline Derivatives as Antitumor Agents Targeting the Colchicine Site on Tubulin

“…32,33) Seven days after inoculation with the tumor cells, mice were randomly divided into 17 groups. The therapeutic regimens (or vehicle) were initiated at day 8 for 14 d as follows, Group 1: mice treated with DMSO (5 mL/kg, intraperitoneally (i.p.))…”