Saxagliptin defers thioacetamide-induced hepatocarcinogenesis in rats: A novel suppressive impact on Wnt/Hedgehog/Notch1 signaling

摘要

Aim: Hepatocellular carcinoma (HCC) is a highly invasive form of hepatic cancer. It is a highly intricate disease with multiple pathophysiological mechanisms underlying its pathogenesis. Materials and methods: The results of the current investigation shed light on the ability of saxagliptin (SAXA) (12.5mg/kg) to defer HCC progression in an experimental model of thioacetamide (TAA)-induced hepatocarcinogenesis. Results: SAXA administration improved liver function biomarkers, with a concomitant histopathological recovery. Mechanistically, the observed hepatoprotective impact was associated with significant suppression of the hepatic content of Wnt3a, β-catenin, Notch1, Smo, and Gli2 and enhanced expression of GSK 3β. Nevertheless, the hepatic expression of PCNA, P53, and cyclin D1 was significantly enhanced, with a parallel increase in the tumor expression of caspase-3. Thus, it appears that SAXA significantly enhanced tumor apoptosis, with concomitant suppression of HCC proliferation. Conclusion: SAXA deferred experimentally-induced HCC via suppressing Wnt/Hedgehog/Notch1 Signaling, with enhanced tumor apoptosis and suppressed proliferation.