Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Department of Interventional Radiology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China.
Environ Toxicol. 2024 Oct;39(10):4677-4688. doi: 10.1002/tox.24295. Epub 2024 May 3.
Glycyrrhizic acid (GA) has effects on anti-hepatic fibrosis, anti-tumor and prevention from hepatocellular carcinoma (HCC) progression. Yet, the capacity of GA to ameliorate the advance of HCC pertinent to nonalcoholic fatty liver disease (NAFLD) remains to be clarified. We used the CCK-8 method to detect the optimal treatment concentration and time for L-02 cells, palmitic acid (PA)-induced L-02 cells and HepG2 cells, and selected 40 μM and 48 h to treat PA-induced L-02 cells and 60 μM for 24 h to treat HepG2 cells. Moreover, functional associations of HepG2 cells were elucidated through various assays. The results showed that GA demonstrated enhances lipid deposition and alleviates the inflammatory response in L-02 cells induced by palmitic acid. Simultaneously, we found that GA inhibits the proliferation, migration, and invasion while promoting apoptosis in HepG2 cells. In pursuit of constructing of HCC model rats, a combination of high-fat diets and diethylnitrosamine was utilized. The results showed that GA significantly decreased the liver index, body weight, liver weight, and the number of nodules in HCC model rats. Moreover, GA mitigated infiltration and heightened apoptosis in these rats. Mechanistically, GA notably attenuated the KKβ/NF-κB pathway in both HepG2 cells and the HCC model rats. In conclusion, GA functions as an inhibitor in the progression of NAFLD-related HCC cells, which might be relevant to the KKβ/NF-κB pathway. Therefore, GA is a potential drug for NAFLD-related HCC treatment.
甘草酸 (GA) 具有抗肝纤维化、抗肿瘤和预防肝细胞癌 (HCC) 进展的作用。然而，GA 改善与非酒精性脂肪性肝病 (NAFLD) 相关的 HCC 的能力仍有待阐明。我们使用 CCK-8 法检测 L-02 细胞、棕榈酸 (PA) 诱导的 L-02 细胞和 HepG2 细胞的最佳治疗浓度和时间，并选择 40μM 和 48 h 来治疗 PA 诱导的 L-02 细胞，60μM 用于 24 h 治疗 HepG2 细胞。此外，通过各种测定法阐明了 HepG2 细胞的功能关联。结果表明，GA 显示出增强脂质沉积并减轻了由棕榈酸诱导的 L-02 细胞中的炎症反应。同时，我们发现 GA 抑制增殖、迁移和侵袭，同时促进 HepG2 细胞凋亡。为了构建 HCC 模型大鼠，我们使用高脂肪饮食和二乙基亚硝胺的组合。结果表明，GA 显著降低了 HCC 模型大鼠的肝指数、体重、肝重和结节数。此外，GA 减轻了这些大鼠的浸润和增强了凋亡。在机制上，GA 显著减弱了 HepG2 细胞和 HCC 模型大鼠中的 KKβ/NF-κB 途径。总之，GA 作为一种抑制剂在 NAFLD 相关 HCC 细胞的进展中起作用，这可能与 KKβ/NF-κB 途径有关。因此，GA 是治疗 NAFLD 相关 HCC 的潜在药物。
