[Effects of octreotide on necrosis of hepatocellular carcinoma xenografts in nude mice].
OBJECTIVE
Octreotide, a kind of somatostatin analogue, may inhibit the growth of hepatocellular carcinoma (HCC). This study was to investigate the mechanism of inducing necrosis of HCC xenografts in nude mice by octreotide.


METHODS
The proliferation of HepG2 cells was determined by MTT assay. Nude mice bearing HepG2 xenografts were treated with octreotide [100 microg times; (kg times; d)(-1)] or normal saline (as control) for eight weeks. The necrosis of HCC was estimated by histology. Vascular endothelial growth factor (VEGF) was detected by immunohistochemistry. Somatostatin receptor 2 (SSTR2) was quantified by Western blot and located with immunohistochemistry.


RESULTS
The proliferation of HepG2 cells was not obviously affected by 24-hour treatment of octreotide (0.1-1000 nmol/L) in vitro. The tumor weight was significantly heavier in octreotide group than in control group [(7.15+/-2.96) g vs. (4.21+/-3.11) g, P<0.05], while the proportion of necrotic volume was significantly higher in octreotide group than in control group [(81.86+/-0.05)% vs. (43.75+/-0.06)%,P<0.05]. In contrast with control group, VEGF was undetected in the xenografts in octreotide group. SSTR2 expression in xenograft sinusoids was similar in both groups.


CONCLUSIONS
With active proliferation of HCC cells, octreotide can induce necrosis in HCC xenografts only through the inhibition of angiogenesis mediated by SSTR2 in the tumor.
Chen
Shuang
S
Division of Peptides, Sichuan University,Chengdu, Sichuan, 610041, People's Republic of China. .
Xie
Yan
Y
Wang
Chun-Hui
CH
Tang
Cheng-Wei
CW
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000187:drug effects; D009336:Necrosis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control; D015282:Octreotide / Q000494:pharmacology*; D017481:Receptors, Somatostatin / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D018931:Antineoplastic Agents, Hormonal; D017481:Receptors, Somatostatin; D042461:Vascular Endothelial Growth Factor A; C093733:somatostatin receptor 2; D015282:Octreotide