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.

中文翻译：

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甘草酸减轻非酒精性脂肪肝疾病相关肝细胞癌的恶性生物学特性

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 进展的能力仍有待阐明。我们采用CCK-8方法检测了L-02细胞、棕榈酸（PA）诱导的L-02细胞和HepG2细胞的最佳处理浓度和时间，并选择40 μM和48 h处理PA诱导的L-02细胞。 02 细胞和 60 μM 处理 24 小时 HepG2 细胞。此外，通过各种测定阐明了 HepG2 细胞的功能关联。结果表明，GA 可以增强棕榈酸诱导的 L-02 细胞中的脂质沉积并减轻炎症反应。同时，我们发现GA抑制HepG2细胞的增殖、迁移和侵袭，同时促进细胞凋亡。为了构建 HCC 模型大鼠，采用了高脂肪饮食和二乙基亚硝胺的组合。结果显示，GA显着降低HCC模型大鼠的肝脏指数、体重、肝脏重量和结节数量。此外，GA 减轻了这些大鼠的浸润并增加了细胞凋亡。从机制上讲，GA 显着减弱 HepG2 细胞和 HCC 模型大鼠中的 KKβ/NF-κB 通路。总之，GA 作为 NAFLD 相关 HCC 细胞进展的抑制剂，可能与 KKβ/NF-κB 通路有关。因此，GA是治疗NAFLD相关HCC的潜在药物。