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01-05-2017 | Original Article

Sorafenib effect on liver neoplastic changes in rats: more than a kinase inhibitor

Authors: Nahla E. El-Ashmawy, Eman G. Khedr, Hoda A. El-Bahrawy, Eslam E. Abd El-Fattah

Published in: Clinical and Experimental Medicine | Issue 2/2017

Abstract

Although sorafenib was approved as antiangiogenic agent in case of hepatocellular carcinoma (HCC), the pathways mediating its antitumorigenic effects were not fully examined in vivo. This study was conducted to elucidate the molecular mechanisms underlying the antineoplastic effect of sorafenib in livers of rats exposed to the hepatocarcinogen diethyl nitrosamine (DENA) regarding oxidative stress, proliferation, and apoptotic pathways. Male albino rats were divided into three groups: normal control, DENA group, and sorafenib group. Sorafenib (10 mg/kg) was given daily to rats orally for 2 weeks, started 6 weeks after DENA (200 mg/kg, single i.p. dose). The histopathological results proved that sorafenib corrected neoplastic changes in the liver as evidenced by a decrease in size of hepatocellular foci. The liver index, glutathione, as well as Bcl-2 were significantly decreased in sorafenib group compared with DENA group. Sorafenib also exhibited antiproliferative effect through suppression of gene expression of cyclin D1 and β-catenin. Thus, the apoptotic and proliferative pathways in HCC could be interrupted by sorafenib, supporting the role of sorafenib as antineoplastic agent and nominating it as a candidate drug for other neoplasms.

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Title: Sorafenib effect on liver neoplastic changes in rats: more than a kinase inhibitor
Authors: Nahla E. El-Ashmawy
Eman G. Khedr
Hoda A. El-Bahrawy
Eslam E. Abd El-Fattah
Publication date: 01-05-2017
Publisher: Springer International Publishing
Published in: Clinical and Experimental Medicine / Issue 2/2017
Print ISSN: 1591-8890
Electronic ISSN: 1591-9528
DOI: https://doi.org/10.1007/s10238-016-0416-3

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