Mechanisms and influence of octreotide-induced regulation of somatostatin receptor 2 on hepatocellular carcinoma.
BACKGROUND
Somatostatin receptors (SSTRs) belong to the family of G protein-coupled receptors. Exposure of G protein-coupled receptors to their agonists induces a rapid decrease in their initial response. The goal of this study is to investigate alteration in SSTR2 by the treatment of SSTR agonist octreotide (OCT) in hepatocellular carcinoma (HCC) and the resulting consequence.


METHODS
Morphology, proliferation and cell cycle of the human HCC cell line (Bel7402) were evaluated. Effect of OCT on HCC growth and development was assessed in vivo. SSTR2 expression was measured by RT-PCR and detected by immunohistochemistry.


RESULTS
Short-term OCT treatment on Bel7402 cells barely changed cell proliferation and morphology, and no apoptosis was induced. The SSTR2 protein level was markedly decreased on Bel7402 cells after exposure to OCT. However, the weight of the HCC xenograft was significantly lower in the OCT treatment group as compared with the control group. In the rat hepatocarcinogenesis model, the mortality and incidence of HCC in the OCT treatment group were remarkably less than those in the control group. Long-term OCT treatment led to increased levels of both SSTR2 mRNA and protein in hepatocytes and HCC cells.


CONCLUSIONS
Short-term OCT treatment could lead to SSTR2 desensitization, resulting in a reduced inhibitory effect on HCC by OCT. However, long-term OCT treatment effectively inhibited the development and growth of HCC probably via resensitization and upregulation of SSTR2.
Hua
Yun-Peng
YP
Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Yin
Xiao-Yu
XY
Peng
Bao-Gang
BG
Li
Shao-Qiang
SQ
Lai
Jia-Ming
JM
Liang
Hui-Zhen
HZ
Liang
Li-Jian
LJ
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D015282:Octreotide / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous
D018931:Antineoplastic Agents, Hormonal; D017481:Receptors, Somatostatin; C093733:somatostatin receptor 2; D015282:Octreotide