The Study Of IL-37 On Autophagy In Hepatocellular Carcinoma Cells And Its Mechanism

Objective To study the effect of IL-37 on autophagy in hepatocellular carcinoma cells and the mechanism.Methods CCK-8 and flow cytometry were used to detect the effect of IL-37 on the cell proliferation of SMMC-7721 and Huh-7 cells.The morphology and quantity of autophagosomes were observed under electron microscope.Western blot method was used to detect the expression of the autophagy protein LC3,Beclin1,p62,the apoptosis protein Bcl-2,Bax,Caspase3,and the protein relating to the AKT/mTOR signaling pathway.The apoptosis of hepatocellular carcinoma was detected by flow cytometry.Results The results of CCK-8 showed that the cell proliferation rate was decreased in IL-37-treated group(p<0.01).Flow cytometry showed that G0/G1 phase arrest(p<0.01)and apoptotic rate(p<0.05)were increased in IL-37-treated group.The electron microscope showed that the number of autophagosome in IL-37-treated group was significantly higher than control group.Western blot showed that the expression of LC3-II/LC3-I、Beclin1、Bax and Caspase3 were increased(p<0.01)and the expression of p62 and Bcl-2 were decreased(p<0.01),and consistent with this,the expression of p-AKT 、 p-mTOR and related proteins were significant decreased(p<0.01)in IL-37-treated group.With the treatment of IGF-1,an agonist of AKT,IL-37 could reversed the inhibitory effect of the agonist of AKT on LC3.Conclusion The cell proliferation of SMMC-7721 and Huh-7 was decreased,and the autophagy and apoptosis rate were increased in IL-37-treated group.IL-37 induced autophagy by inhibiting the PI3K/AKT/mTOR pathway.This study demonstrated that IL-37 suppress the cell proliferation by inducing autophagy and apoptosis in SMMC-7721 and Huh-7 cells.This work is important for the further study of IL-37 and provides evidence for targeted therapy.