A somatostatin analogue, octreotide, inhibits the occurrence of second primary tumors and lung metastasis after resection of hepatocellular carcinoma in mice.
Occurrence of second primary tumors and metastasis remains the major obstacles to prolonged survival of patients with primary hepatocellular carcinoma (HCC). A somatostatin analogue, octreotide, has been previously reported to inhibit the growth of human HCC xenografts in nude mice through its anti-angiogenic activity. It is therefore important to investigate whether octreotide could prevent second primary hepatomas or distant metastasis following resection of primary HCC. In this study, nude mice, bearing the human HCC xenografts with highly metastatic potential (LCI-D20) in the left liver lobe, underwent tumor resection, and received intraperitoneal administration of octreotide or saline as a control for 35 consecutive days. Compared with the control group, octreotide at the doses of 100 and 200 microg/kg/day significantly inhibited the growth (P < 0.001 and P < 0.001, respectively) and incidence of second primary tumors (P = 0.016 and P = 0.001, respectively), decreased lung metastasis (P < 0.001 and P < 0.001, respectively), and prolonged the life span (P = 0.029 and P = 0.006, respectively). Moreover, intratumoral angiogenesis quantified by microvessel density as well as serum and tissue vascular endothelial growth factor (VEGF) levels were considerably decreased in octreotide-treated animals compared to the control animals. These findings suggest that octreotide may prevent the occurrence of second primary hepatomas and lung metastasis after resection of primary HCC, which may be partially attributed to down-regulation of VEGF and subsequent reduction in tumor angiogenesis. Octreotide administration may be useful as an adjuvant therapy to improve survival of patients with HCC.
Jia
Wei-Dong
WD
Centre for the Study of Liver Cancer, Anhui Provincial Hospital, Anhui Medical University, Hefei, China.
Xu
Ge-Liang
GL
Wang
Wei
W
Wang
Zhi-Hua
ZH
Li
Jian-Sheng
JS
Ma
Jin-Liang
JL
Ren
Wei-Hua
WH
Ge
Yong-Sheng
YS
Yu
Ji-Hai
JH
Liu
Wen-Bin
WB
D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000098:blood supply / Q000473:pathology* / Q000601:surgery*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000097:blood / Q000517:prevention & control* / Q000556:secondary*; D008297:Male; D051379:Mice; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D016609:Neoplasms, Second Primary / Q000097:blood / Q000517:prevention & control*; D015282:Octreotide / Q000494:pharmacology*; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D017481:Receptors, Somatostatin; D042461:Vascular Endothelial Growth Factor A; D013004:Somatostatin; D015282:Octreotide