Glycyrrhizic acid attenuates the malignant biological properties of nonalcoholic fatty liver disease‐related hepatocellular carcinoma

Abstract 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.