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

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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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Acknowledgments

Authors gratefully acknowledge Dr. Mona A. Yehia, Professor of Histochemistry and Cell Biology, Medical Research Institute, Alexandria, for conducting and interpreting the histopathological examination.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt

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

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  1. Nahla E. El-Ashmawy
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  2. Eman G. Khedr
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  3. Hoda A. El-Bahrawy
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  4. Eslam E. Abd El-Fattah
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Correspondence to Eslam E. Abd El-Fattah.

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This manuscript was made only for research studies associated with master thesis discussion for the corresponding author. Eslam E. Abd El-Fattah declare no conflict of interest.

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El-Ashmawy, N.E., Khedr, E.G., El-Bahrawy, H.A. et al. Sorafenib effect on liver neoplastic changes in rats: more than a kinase inhibitor. Clin Exp Med 17, 185–191 (2017). https://doi.org/10.1007/s10238-016-0416-3

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  • DOI: https://doi.org/10.1007/s10238-016-0416-3

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