Antiangiogenic effect of octreotide inhibits the growth of human rectal neuroendocrine carcinoma.
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.


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/mm(2) treated vs. 341.4 +/- 56.6/mm(2) 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.
Koizumi
Michihiro
M
First Department of Surgery, Nippon Medical School, Tokyo, Japan. michihiro@msh.biglobe.ne.jp
Onda
Masahiko
M
Tanaka
Noritake
N
Seya
Tomoko
T
Yamada
Takeshi
T
Takahashi
Yoshiyuki
Y
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy* / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000097:blood; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008222:Lymphokines / Q000097:blood; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009336:Necrosis; D015282:Octreotide / Q000494:pharmacology* / Q000627:therapeutic use; D017481:Receptors, Somatostatin / Q000378:metabolism; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D018931:Antineoplastic Agents, Hormonal; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D017481:Receptors, Somatostatin; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005346:Fibroblast Growth Factors; D015282:Octreotide