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角鲨胺通过抑制PI3K/AKT信号通路在二乙基亚硝胺诱导的肝细胞癌中的化学预防潜力

Chemopreventive potential of goniothalamin in diethylnitrosamine-induced hepatocellular carcinoma through the suppression of P13K/AKT signalling pathway.

作者信息

Li Jie, Zhan Dong, Chen Cui, Li Rongfu, Zhu Fang-Qing

机构信息

Hepatobiliary and Pancreatic Surgery, Fuyang People's Hospital in Anhui Province, Fuyang 236000, Anhui, China.

Human Anatomy Laboratory of Experimental Teaching Centre, School of Basic Medical Sciences, Kunming Medical University, Kunming 650500, Yunnan, China.

出版信息

Korean J Physiol Pharmacol. 2024 Nov 1;28(6):539-547. doi: 10.4196/kjpp.2024.28.6.539.

Abstract

Liver cancer is the most lethal form of cancer and carries a high risk of death around the world. Goniothalamin (GTN) is a styryl-lactone that possesses antiproliferative and apoptotic activity. The molecular action of GTN is not yet fully evaluated. Thus, our research has been intended to assess the chemopreventive and apoptotic activities of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. Rats were separated into 4 groups: control, DEN only, DEN + GTN (30 mg/kg bw), and GTN (30 mg/kg bw) alone. We evaluated body weight, liver weight, tumor incidence, hepatic toxic markers, antioxidants, inflammatory cytokines, histopathology, immunohistochemistry, and Western blot studies. DEN lessened body weight, antioxidants, and apoptosis, whereas it elevated tumor incidence, toxic markers, cytokines, and Bcl-2 expression. GTN treatment maintains body weight, liver weight, and antioxidant levels, and it also prevents tumor incidence, oxidative stress, toxic markers, pro-inflammatory cytokines, and histological changes. It triggers apoptosis by constraining Bcl-2 and elevating caspase-3 levels. GTN also attenuated the P13K/ AKT signaling which enhanced apoptosis. These findings revealed that GTN subdues the P13K/AKT pathway and has auspicious chemopreventive and apoptotic actions in DEN-induced HCC. Therefore, GTN would be suggested as a new medicine in natural remedies for liver cancer.

摘要

肝癌是最致命的癌症形式,在全球范围内具有很高的死亡风险。角鲨胺(GTN)是一种具有抗增殖和凋亡活性的苯乙烯基内酯。GTN的分子作用尚未得到充分评估。因此,我们的研究旨在评估二乙基亚硝胺(DEN)诱导的大鼠肝细胞癌(HCC)的化学预防和凋亡活性。将大鼠分为4组:对照组、仅给予DEN组、DEN + GTN(30 mg/kg体重)组和单独给予GTN(30 mg/kg体重)组。我们评估了体重、肝脏重量、肿瘤发生率、肝脏毒性标志物、抗氧化剂、炎性细胞因子、组织病理学、免疫组织化学和蛋白质印迹研究。DEN降低了体重、抗氧化剂水平和细胞凋亡,而提高了肿瘤发生率、毒性标志物、细胞因子和Bcl-2表达。GTN治疗可维持体重、肝脏重量和抗氧化剂水平,还可预防肿瘤发生率、氧化应激、毒性标志物、促炎细胞因子和组织学变化。它通过抑制Bcl-2和提高caspase-3水平来触发细胞凋亡。GTN还减弱了增强细胞凋亡的P13K/AKT信号传导。这些发现表明,GTN抑制P13K/AKT途径,对DEN诱导的HCC具有良好的化学预防和凋亡作用。因此,GTN有望成为肝癌天然疗法中的一种新药。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7a9/11519720/ab3f7842546a/kjpp-28-6-539-f1.jpg

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