Regulation of ULK1 on the growth of hepatocellular carcinoma cells and the effect of its inhibitors on cell proliferation
Objective To investigate the expression and prognosis of UNC-51-like kinase 1(ULK1)in hepatocellular carcinoma(HCC),and whether knocking down ULK1 or inhibiting the activity of ULK1 kinase can inhibit the proliferation of hepatocellular carcinoma cells,induce apoptosis and enhance the sensitivity of oxaliplatin.Methods The expression and prognosis of ULK1 in pan-cancer and HCC were analyzed in online database.Quantitative real-time polymerase chain reaction was used to verify the knock-down efficiency of different ULK1 knock-down sequences.CCK8 method was used to detect the effect of knockout ULK1 on the proliferation of hepatocellular carcinoma cell line HepG2.CCK8 method was used to detect the effects of ULK1 inhibitor and oxaliplatin on the proliferation of HepG2 cells.Flow cytometry was used to detect the effect of oxaliplatin combined with ULK1 inhibitor on apoptosis of HepG2 cells.Immunoblotting experiments were conducted to detect the effect of oxaliplatin combined with ULK1 inhibitors on autophagy in HepG2 cells.Results ULK1 was highly expressed in HCC and negatively correlated with the prognosis of patients.The ULK1 gene was successfully knocked down in HepG2 cells.Knocking down ULK1 can reduce the proliferation of HepG2 cells.The combination of ULK1 inhibitor and oxaliplatin can inhibit the proliferation of HepG2 cells and increase the number of apoptosis of HepG2 cells.The mechanism may be related to enhancing autophagy of HepG2 cells.Conclusion Knocking down ULK1 or using ULK1 inhibitor can inhibit the proliferation and induce apoptosis of HepG2 cells,or may enhance the toxicity of chemotherapy drugs,and its mechanism may be related to the regulation of autophagy.