Regulation of octreotide on SSTR2 expression in hepatocellular carcinoma

AIM: To observe the regulation of octreotide (OCT) on the expression of somatostatin receptor 2 (SSTR2) in Bel7402 hepatocellular carcinoma (HCC) cells, and the inhibition effect of OCT on the growth of HCC. METHODS: The effect of OCT on proliferative ability of Bel7402 cells was observed by MTT assay. The cell form was observed by light invert microscope. The adhesive and invasive ability was detected by cell adhesion and migration experiments. The cell cycle, SSTR2 expression of 7402 cells were determined by immunofluorescence flow cytometry. Nude mice bearing xenografts in situ were treated with OCT or saline control for 7 weeks since tumor implantation. The immunohistochemistry for SSTR2 was performed. SSTR2 mRNA expression in cell line and xenografts was measured by semi-quantitative RT-PCR. RESULTS: After OCT treatment, the proliferative ability and cell form of 7402 cells didn't change significantly. The adhesive and invasive ability decreased significantly. The ratio of cells in resting state (G₀/G₁) increased, but no apoptosis peak was observed. The SSTR2 expression on 7402 cell membranes decreased significantly. SSTR2 expression in cell line of OCT group was higher than control group, but there was no significant difference between them. The mean tumor weight in mice given OCT was significantly lower than that in control group. SSTR2 immunostaining in tumor cells of treatment group showed stronger positivity, compared with control group. SSTR2 mRNA expression in xenografts after OCT treatment was significantly higher than that in control group. CONCLUSIONS: OCT inhibits the growth of HCC through SSTR2. SSTR2 is regulated by its ligand, the long-term OCT treatment increases the SSTR2 expression and enhances the effect of inhibiting HCC, however, short-term treatment may induces its desensitization and the decrease in anti-tumor effect.