沙格列汀延缓硫代乙酰胺诱导的大鼠肝癌发生：对 Wnt/Hedgehog/Notch1 信号的新抑制作用。
Saxagliptin defers thioacetamide-induced hepatocarcinogenesis in rats: A novel suppressive impact on Wnt/Hedgehog/Notch1 signaling.
机构信息
Dep. of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; Dep. of Pharmacology, Faculty of Pharmacy, Horus University-Egypt, New Damietta, Egypt.
Dep. of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
出版信息
Environ Toxicol Pharmacol. 2021 Aug;86:103668. doi: 10.1016/j.etap.2021.103668. Epub 2021 May 1.
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) (12.5 mg/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.
目的
肝细胞癌（HCC）是一种高度侵袭性的肝癌。它是一种非常复杂的疾病，其发病机制涉及多种病理生理机制。
材料和方法
本研究的结果揭示了沙格列汀（SAXA）（12.5mg/kg）在硫代乙酰胺（TAA）诱导的肝癌发生实验模型中延缓 HCC 进展的能力。
结果
SAXA 给药改善了肝功能生物标志物，并伴有组织病理学恢复。从机制上讲，观察到的肝保护作用与 Wnt3a、β-连环蛋白、Notch1、Smo 和 Gli2 的肝含量显著抑制以及 GSK 3β 的表达增强有关。然而，PCNA、P53 和细胞周期蛋白 D1 的肝表达明显增强，同时肿瘤中 caspase-3 的表达增加。因此，SAXA 似乎通过抑制 Wnt/Hedgehog/Notch1 信号通路显著增强肿瘤细胞凋亡，同时抑制 HCC 增殖。
结论
SAXA 通过抑制 Wnt/Hedgehog/Notch1 信号通路延缓了实验诱导的 HCC，同时增强了肿瘤细胞凋亡并抑制了增殖。
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