Protective effect of Sorafenib against 1,2-Dimethylhydrazine-induced colorectal cancer in Balb/c Mice

Abstract

Author(s): M. Al Hassan, M. Al Battal, J. Usta and J. Borjac*

Colorectal Cancer (CRC) is the third leading cause of cancer death in the world whose incidence is progressively rising in developing nations. It is treated with both chemotherapeutic and immunotherapeutic agents. Sorafenib is a broad-spectrum multikinase inhibitor proven to be effective in treating different types of carcinoma, including liver, thyroid, renal, and breast cancers. This study aimed to investigate the effect of Sorafenib against 1,2-dimethylhydrazine (DMH)-induced CRC in mice. Mice were injected with DMH (20 mg/kg) over 12 weeks to induce the cancer. Mice were treated with Sorafenib (30 mg/Kg for 5 days). Colon tissues were examined by histological analysis, and gene expression level of key players involved in the Wnt signaling pathway were assessed using RT-PCR. Our results showed that Sorafenib restored the normal histology and structure of colonic tissue. Sorafenib downregulated the expression level of Wnt5a and Cyclin D1 and upregulated that of APC, GSK-3β and β catenin compared to untreated control. In conclusion, Sorafenib inhibits DMH-induced CRC by targeting the Wnt signaling pathway.

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