الفهرس 
IntroductionOnly 14 pages are availabe for public view
Abstract
The present study aimed to evaluate the anti-tumor activity of SB-431542, as well as their impact on cisplatin (CP)-evoked chemo preventive effects, in EAC model in mice. In this study, we evaluated TGF-β and TGF-βR1 levels in response to treatment with CP or SB-435142 or their combinations. In addition, correlations were made between TGF-βR1 and the dissociation of TGF precursor molecule in response to treatment with SB-435142 mainly. CP is a commonly used cytotoxic agent in the treatment of numerous solid tumors in various clinical settings. However, the clinical usefulness of CP is limited by the development of serious nephrotoxicity, a side effect that is also reproducible in various animal models. The ability of SB-435142 to protect rats against CP-induced nephrotoxicity was also evaluated. This is the first study to declare the cytotoxic effect of SB-431542 on EAC models. SB-431542 was previously studied as a potent antitumor agent for different human cancers. In this study we could conclude that SB-431542 induced cytotoxic effects on Ehrlich ascites carcinoma cells by several mechanisms including antioxidant and TGF-β1 inhibition mechanisms. In addition, we also could conclude that blocking TGF-βR1 by SB-431542 results in a dose dependent amelioration of the impairment of renal tissues function and structure in rats treated with cisplatin via multiple mechanisms including: (1) reducing cisplatin-induced oxidative stress, as indicated by reducing renal MDA levels and restoring the activity of renal SOD; (2) blocking cisplatin-induced elevation of renal inflammatory cytokines such as sCD93; (3) reducing cisplatin-induced elevation of renal fibrosis markers as TGF-1β; and (4) inhibiting cisplatin-induced activation of renal caspase-3.