Antiangiogenic Effect of Octreotide Inhibits the Growth of Human Rectal Neuroendocrine Carcinoma

Abstract

Background: Somatostatin and its analogues have antitumor effects on foregut and midgut neuroendocrine (NE) tumors, but their effect on hindgut NE tumors is unclear. We examined the effect of the somatostatin analogue, octreotide, on human rectal NE carcinoma. Materials and Methods: Expression of somatostatin receptor (sst) on NE carcinoma was examined by immunohistochemical staining. Octreotide was added in cell culture medium in order to investigate antiproliferative effect toward NE carcinoma in vitro. Octreotide was administered for 6 weeks to nude mice xenografted with NE carcinoma. We investigated the effect of octreotide on the tumor histologically. The plasma levels of VEGF and bFGF were measured. Results: The NE carcinoma and endothelial cells expressed sst. Octreotide induced NE carcinoma to apoptosis in vitro and in vivo. Octreotide-treated tumors had a massive necrotic area (62.7 ± 19.3% treated vs. 39.7 ± 20.34% untreated, p < 0.05). Microvessels in the treated tumor were decreased (264.0 ± 48.2/mm² treated vs. 341.4 ± 56.6/mm² untreated, p < 0.05). The plasma levels of VEGF and bFGF were reduced by octreotide. Conclusions: Octreotide induces rectal NE carcinoma to apoptosis and inhibits angiogenesis in the tumor. These result in tumor necrosis. Octreotide has an antitumor effect on rectal NE carcinoma.