Key Moleculars Of Sinomenine Inhibiting Proliferation Of Hepatocellular Carcinoma Cells: An Experimental Study

Background: Hepatocellular carcinoma(HCC)is the most common liver tumor.The global incidence of liver cancer is increasing year by year.In recent years,with the application of molecular targeted drugs in clinical practice,the median survival of a large number of patients with advanced HCC has been improved to some extent,but overall,the efficacy of HCC is still not satisfactory,so we urgently need to find drugs that can prolong the survival of patients with HCC.In our previous studies,sinomenine has been found to inhibit the activity of liver cancer cell lines,but the molecular mechanism by which sinomenine exerts its effect is still unclear.Objective: To explore the effects of sinomenine in vivo and in vitro on liver cancer,as well as the possible mechanisms related.Method: In this study,we firstly determined the IC50 value of sinomenine on HCC cells by MTT method,and calculated the safe dose of sinomenine in vivo based on this value.The effect of sinomenine on HCC in vivo and in vivo was detected by xenograft tumor experiment in nude mice,full-field cell analyzer and MTT method.Gene microarray,Q-PCR and Western blot were used to detect the expression differences of genes and proteins in HCC cells before and after sinomenine treatment.Finally,gene knockdown,cloning and formation experiments,FACS cell apoptosis detection,scratches and transwell chamber were used to verify the role of specific genes in HCC cells.Results: Sinomenine can inhibit the proliferation of hepatocellular carcinoma cells and the growth of xenograft tumor in nude mice.The expression of genes related to proliferation and apoptosis of HCC cells after sinomenine treatment has been changed to different degrees,among which the expression of related molecules in the Interferon Signaling pathway has been changed,and the gene significantly different from the expression of proliferation-related genes is TRIM29.The knockdown of TRIM29 can increase apoptosis of HCC cells and inhibit the metastatic ability of tumor cells.Conclusion: Sinomenine may inhibit the proliferation of hepatocellular carcinoma cells and xenograft tumor growth in nude mice by regulating the expression of the downstream gene TRIM29 through the type Ⅱ Interferon Signaling pathway(IFNγ).It was also found that the gene TRIM29 was closely related to the proliferation ability of HCC cells,and knockdown of TRIM29 could reduce the proliferation,increase the apoptosis,and weaken the metastasis ability of HCC cells,but had no significant effect on the migration ability of HCC cells.Through the study of the mechanism of sinomenine in hepatocellular carcinoma,it provides a new direction for the treatment of hepatocellular carcinoma.