TITLE:
Assessment of the Safety of Olmesartan in Combination with Sorafenib in Mice Bearing Ehrlich’s Ascites Carcinoma
AUTHORS:
Mohammad M. Abd-Alhaseeb, Sawsan A. Zaitone, Soad H. Abou-El-Ela, Yasser M. Moustafa
KEYWORDS:
Mice; Ehrlich’s Ascites Carcinoma; Olmesartan; Sorafenib
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.4 No.8,
October
29,
2013
ABSTRACT: Sorafenib
was the first multikinase inhibitor to be approved for use in metastatic renal
cell carcinoma. Olmesartan medoxomil used in treatment of hypertension and was
reported to inhibit angiogenesis in several models. The present study was
designed to assess the safety of a combination of sorafenib plus olmesartan
compared to monotherapies in mice bearing Ehrlich’s ascites carcinoma cell
line. Mice were divided to seven groups, 1) normal mice, 2) Ehrlich’s ascites carcinoma
control, 3 - 5) olmesartan (3, 10, 30 mg/kg/day), respectively, 6) sorafenib
(30 mg/kg/day) and 7) the combination group: mice received olmesartan (30
mg/kg/day) plus sorafenib. All drug treatments continued for 21 days. At the
end of the experiment, a complete blood count was performed and kidney and
liver functions were estimated. The combination therapy produced a
non-significant change in most of the measurements of complete blood count and
liver enzymes when compared to normal animals. On the other hand, the combined
therapy significantly increased blood urea nitrogen when compared to normal
group but did not change the serum creatinine level. Concomitant administration
of olmesartan with sorafenib did not significantly augment the toxicity of the
later. Therefore; olmesartan might be a safe candidate with sorafenib in
treatment of cancer if clinical data proved the benefit of this combination.