الفهرس 
Introduction & Aim of the WorkOnly 14 pages are availabe for public view
 |  | from | 270 |  |  |
| | | from | 270 | | |
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. Hepatocellular carcinoma can be induced by multiple etiologies, is influenced by many risk factors, and has complex pathogenesis. Wingless-related integration site (Wnt/β-catenin) and Notch signaling pathways were found to be highly implicated in the pathogenesis of HCC. Therefore, targeting Wnt/β-catenin and Notch signaling potentiates a novel avenue for HCC treatment. Niclosamide (NIC) is a drug used for 50 years for the treatment of anthelmintic teniasis. Its mechanism of action is attributed to the uncoupling of oxidative phosphorylation in the tapeworm mitochondria. Recently, new biological activities related to cancer diseases have been attributed to this molecule, which perhaps make this drug one of the most promising candidates for repositioning for new therapeutic indications. However, the mechanism of antitumor action of NIC still needs a better understanding, which is hampered by its low water solubility and hence its bioavailability. Therefore, the present study aimed to develop a novel oral NIC nanoformulation employing pluronic polymer nanoparticles to improve its poor water solubility and study its antitumor effect as compared to its native form in thioacetamide (TAA)-induced HCC rat model. Moreover, the present study aimed to understand the antitumor mechanisms of the newly developed NIC nanoformulation, niclosamide-loaded pluronic nanoparticles (NIC-NPs), through targeting Wnt/β-catenin, as well as Notch signaling pathways in experimentally induced HCC in rats. The novel NIC-NPs improved liver functions, reduced AFP level and showed improved anticancer and proapoptotic activities compared to drug alone. The inhibitory effect of NIC on Wnt/β-catenin and Notch signaling pathways was potentiated by the NIC-NPs formulation. We can conclude that the novel nanoparticle formulation has indeed ameliorated the efficacy of the poorly soluble NIC and could be considered a promising approach for targeting HCC.