Somatostatin inhibits development of hepatocellular carcinoma through regulation of SSTR2 and Cmet expression

Objective To observe the inhibitiory effects and mechanism of Somatostatin (SST) on the growth of Bel7402 hepatocellular carcinoma (HCC) cell line and HCC xenografts in nude mice.Methods The effect of SST on proliferative ability of Bel7402 cells was observed by methabenzthiazuron (MTT) assay and the changes in cell morphology under light microscopy.The adhesive and invasive ability of 7402 cells was measured via cell adhesion and migration experiments.The cell cycle,the Cmet (hepatocyte growth factor repceptor) and SST receptor 2 (SSTR2) expression of 7402 cells were detected by immunofluorescence flow cytometry.Nude mice bearing xenografts of cell line were treated with SST or saline (control group) for 7 weeks until tumor implantation.The immunohistochemistry for SSTR2 and Cmet was performed.Results After the treatment withSST,the proliferative ability and cell morphology of 7402 cells didn't change signiFicantly.The adhesive and invasive ability was decreased significantly.The ratio of cells in resting state (G0/G1) was increased,but no apoptosis peak was observed.The Cmet and SSTR2 expression on 7402 cells membranes was decreased significantly.The mean tumor weight in mice treated with SST was significantly less than that of the control group.In immunohistochemistry,SSTR2 immunostaining in tumor cells of treatment group showed stronger positivity than that of control group.Conveersely,the intensity of Cemt immunolabeling was decresed obviously after the treatment.Conclusion SST could inhibit the growth of HCC through combining with SSTR.The long-term SST treatment can increase the SSTR2 expression and enlarge the effect of inhibiting HCC though short-term treatment may induces its desensitization.The decrease of the Cmet expression in HCC cells may play an important role in SST inhibiting HCC.