Chemopreventive effect of leflunomide against Ehrlich's solid tumor grown in mice: Effect on EGF and EGFR expression and tumor proliferation

• Published in: Life sciences (1973) 2015-11, Vol.141, p.193-201
• Main Authors: Bahr, Hoda I., Toraih, Eman A., Mohammed, Eman A., Mohammad, Hala M.F., Ali, Eman A.I., Zaitone, Sawsan A.
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenesis Inhibitors - pharmacology; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Antineoplastic Agents - pharmacology; Carcinoma, Ehrlich Tumor - metabolism; Carcinoma, Ehrlich Tumor - pathology; Carcinoma, Ehrlich Tumor - prevention & control; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Ehrlich's carcinoma; Epidermal growth factor; Epidermal Growth Factor - biosynthesis; Epidermal Growth Factor - genetics; Female; Gene Expression Profiling; Immunohistochemistry; Isoxazoles - pharmacology; Leflunomide; Mice; Platelet Endothelial Cell Adhesion Molecule-1 - biosynthesis; Platelet Endothelial Cell Adhesion Molecule-1 - genetics; Proliferating Cell Nuclear Antigen - biosynthesis; Receptor, Epidermal Growth Factor - biosynthesis; Receptor, Epidermal Growth Factor - genetics; Tumor Necrosis Factor-alpha - blood; Tumor proliferation
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2015.10.003

i) Aims: The current study aimed to examine the effect of leflunomide on tumoral expression of epidermal growth factor and its receptor (EGFR) in Ehrlich's ascites carcinoma (EAC) grown in mice. ii) Materials and methods: Mice were injected subcutaneously with EAC cells and allocated into four groups; Group i: EAC control group. Groups ii–iv: mice treated with leflunomide (3, 10 or 30mg/kg/day, p.o.), respectively. Pharmacologic treatments were initiated at day 8 and continued for 14days. iii) Key findings: Treatment with leflunomide evoked antitumor properties as indicated by reduction in tumor mass, histopathological score, number of intratumoral PCNA immunopositive nuclei. Leflunomide (3, 10 or 30mg/kg) exerted an anti-inflammatory effect as indicated by the reduction in serum tumor necrosis factor-α. Furthermore, leflunomide demonstrated anti-angiogenic activity which was expressed as a decline in serum vascular endothelial growth factor and down-regulation of intratumoral EGF protein and mRNA expression as well as EGFR expression in addition to suppression of immunostaining for the endothelial marker, CD31. iv) Significance: Taken together, the present results demonstrated that leflunomide possessed anti-angiogenic and anti-proliferative activity against EAC solid tumors that might be correlated to down regulation of EGF and EGFR. Further, the current data indicated that leflunomide may have utility in the management of human cancer.