Inhibition effects of octreotide on the growth of hepatocellular carcinoma in vitro and in vivo
Objective: To investigate the effects of somatostatin analogue octreotide on the proliferation and apoptosis of human hepatocellular carcinoma (HCC) cell line as well as the growth of HCC xenografts in nude mice. Methods The effects of octreotide on the proliferation and apoptosis of SMMC-7721 HCC cells was measured by 3H-thymidine incorporation into DNA and the TdT-mediated dUTP nick end labeling assay (TUNEL) or flow cytometric assay separately. Nude mice bearing xenografts of the cell line were treated with octreotide or saline as a control daily until eight weeks after tumor implantation. Results Incubation with octreotide decreased 3H-thymidine incorporation into DNA of SMMC-7721 cells by～50% at a concentration of 1μM. The inhibit effect of octreotide showed a concentration dependence. After 96h incubation, total cell count was decreased 52.2% compared with control. When cells were treated by octreotide at 1×10-6mol/L for 24 hours, the apoptosis rates was (15.2±2.4)%. At necropsy, in mice given octreotide, the mean tumor weight were significantly lower than that of control group(0.27±0.05 vs 0.85±0.37,P<0.01). The inhibition rate of tumor in vivo at 2 months was 68.2%. Conclusion Octreotide is effective in inhibiting growth of HCC both in vivo and in vitro significantly. The mechanisms of antineoplastic effect action may involved in inhibiting DNA synthesize and inducing apoptosis of tumor cells.