title: Mechanisms and influence of octreotide-induced regulation of somatostatin receptor 2 on hepatocellular carcinoma.
abstract: 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.
authors: Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Yun-Peng
authors: YP
authors: Hua
authors: Xiao-Yu
authors: XY
authors: Yin
authors: Bao-Gang
authors: BG
authors: Peng
authors: Shao-Qiang
authors: SQ
authors: Li
authors: Jia-Ming
authors: JM
authors: Lai
authors: Hui-Zhen
authors: HZ
authors: Liang
authors: Li-Jian
authors: LJ
authors: Liang
mesh_terms: 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
chemical_list: D018931:Antineoplastic Agents, Hormonal; D017481:Receptors, Somatostatin; C093733:somatostatin receptor 2; D015282:Octreotide