Liraglutide promotes apoptosis of HepG2 cells by activating JNK signaling pathway.

OBJECTIVE: To study the effect and mechanism of liraglutide on the apoptosis of human hepatocellular carcinoma HepG2 cells. MATERIALS AND METHODS: HepG2 cell was treated with different concentrations of liraglutide at 0, 1, 10, 100, and 1000 nmol/L. The effect of liraglutide on HepG2 proliferation was detected by Cell Counting Kit-8 (CCK-8) method; the effect of liraglutide on the protein expression of c-Jun NH2-terminal Kinase (JNK) and phosphorylated JNK (p-JNK) was detected by Western blot; the degree of HepG2 apoptosis was observed by flow cytometry, and JNK pathway blocker SP600125 was used to further confirm that liraglutide promoted HepG2 apoptosis by regulating JNK signaling pathway. RESULTS: The proliferation inhibition rate of HepG2 cells increased with time and the increase in the concentration of liraglutide. The proliferation inhibition rate was the strongest when cultured for 48 h, and the IC50 (half maximal inhibitory concentration) was about 100 nmol/L of liraglutide. 100 nmol/L liraglutide was selected as the intervention condition for subsequent use of SP600165. The apoptosis rate of HepG2 cells increased with the increase of liraglutide's concentration. The apoptosis rate of HepG2 cells at blocker SP600125+100 nmol/L liraglutide was significantly lower than that at 100 nmol/L liraglutide alone (p<0.05). There was no significant difference in the expression of JNK protein in HepG2 cells at different concentrations of liraglutide (p>0.05). There was no significant difference in the expression of JNK protein in HepG2 cells using JNK pathway blocker SP600125 (p>0.05), while using JNK pathway blocker SP600125 significantly up-regulated the expression of p-JNK protein in HepG2 cells than 100 nmol/L of liraglutide alone (p<0.05). CONCLUSIONS: Liraglutide can promote the apoptosis of hepatocellular carcinoma HepG2 cells in a dose-dependent manner, and its mechanism may act by promoting the activation of the JNK signaling pathway.