Ginsenoside Rg3 and sorafenib combination therapy relieves the hepatocellular carcinomaprogression through regulating the HK2-mediated glycolysis and PI3K/Akt signaling pathway

Abstract

ABSTRACT Hepatocellular carcinoma (HCC) is the most common pathological type of primary hepatic carcinoma. This study investigated the effects of ginsenoside Rg3 (Rg3) and sorafenib (SFN) combination therapy on HCC progression. The HCC-related data were obtained from TCGA database, and the data of HK2 mRNA, clinicopathological features, and survival outcomes were extracted using R Programming 4.0. The human hepatoma cell lines HepG2 and Bel7404 were used. Cell viability was tested using the MTT assay. Glucose consumption and lactate levels of HCC cells were detected using the corresponding kits. Western blotting was used to determine the protein expression of HK2, PI3K, and Akt. HK2 was overexpressed in patients with HCC. Compared with patients with overexpressed HK2, those with low levels of HK2 achieved a longer survival time. In addition, the Rg3 and SFN combination therapy significantly reduced cell viability, glucose consumption, lactate levels, and protein expression of HK2, PI3K, and Akt in HCC cells. Additionally, the Rg3 and SFN combination therapy exhibited a better effect than the single drug group. Inhibition of the PI3K/Akt signaling pathway or exogenous lactate intervention reversed the effects of Rg3 and SFN combination therapy in HCC cells. In conclusion, Rg3 has a synergistic effect on the sensitivity of HepG2 and Bel7404 hepatoma cells to SFN, which is related to HK2-mediated glycolysis and the PI3K/Akt signaling pathway.