The Effect Of Metformin On The Growth Of Human Hepatocarcinoma Transplanted Subcutaneously In Nude Mice And The Expression Of Inflammation-related Proteins In The Tumor Microenvironment

Objective:The object of this study was to observe the inhibitory effect of metformin on the growth of human hepatocellular carcinoma xenografts in nude mice,and to explore the molecular mechanism of metformin in inhibiting the expression of EMT-related proteins SLUG,TWSIT and ?-catenin by improving TNF-?,MMP-9 and regulating EGF-NEDD9 pathway in tumor microenvironment.Methods:BALB/c nude mice were used to establish the subcutaneous transplantation model of human hepatocellular carcinoma in nude mice,and were randomly divided into model group?metformin group and chemotherapy group.Metformin group was given 6.25mg/25 g body weight by intragastric administration,model group was given the same amount of saline for 21 days,chemotherapy group was given 0.6 mg/25 g body weight according to 5-FU 1.25 mg/mL,cisplatin 0.25 mg/mL was given 0.1 mg/25 g body weight,injected once every 7 days,three times.Execute nude mice 21 days later,subcutaneous transplanted tumors were removed and their volume and weight were measured to calculate the inhibition rate.Western blot was used to detect the expression of TNF-?,MMP-9,EGF-NEDD9,SLUG,TWSIT and ?-catenin in subcutaneous transplanted tumors.Results:Compared with the model group,the volume and weight of the tumors in metformin group and chemotherapy group were significantly inhibited(P < 0.001,P<0.05);Western blot results showed that the expressions of TNF-a,MMP-9,EGF,NED9 and EMT-related proteins SLUG,TWSIT,?-catenin in metformin group and chemotherapy group were significantly lower than those in the model group(P < 0.05).Conclusion:Metformin can significantly inhibit the growth of human hepatocellular carcinoma xenografts in nude mice.Metformin can reduce the expression of TNF-a and MMP-9proteins in the xenografts of human hepatocellular carcinoma by down-regulating theexpression of TNF-a and MMP-9 proteins,improve the inflammation of tumor microenvironment,and reduce the expression of EMT-related proteins through EGF-NEDD9 pathway,thus reducing the invasiveness and metastasis..