Inhibitory effect of octreotide on gastric cancer growth via MAPK pathway

World J Gastroenterol. 2003 Sep;9(9):1904-8. doi: 10.3748/wjg.v9.i9.1904.

Abstract

Aim: Somatostatin and its analogues may suppress the growth of various tumor cells. However, the effect of octreotide on growth of gastric adenocarcinoma is still largely unknown. This study was to explore if octreotide could inhibit the growth of gastric adenocarcinoma and its probable mechanisms.

Methods: Proliferation of gastric cancer cell line affected by octreotide was determined by (3)H-thymidine incorporation. After xenografts of human gastric cancer were implanted orthotopically in stomach, nude mice were administrated octreotide for 8 weeks. The mRNA of somatostatin receptor in the SGC-7901 cells was detected by reverse transcription polymerase chain reaction technique. Extracellular signal-regulated protein kinase and c-Fos in gastric cancer tissues were measured by immunohistochemistry and Western blot. Activator protein-1 binding activity was examined by electrophoretic mobility sift assay.

Results: (3)H-thymidine incorporation into SGC-7901 cells was significantly decreased by octreotide in a concentration dependent manner. Either size or weight of tumors treated with octreotide was significantly reduced in vivo. The inhibition rate for tumor was 62.3 % in octreotide group. The genes of somatostatin receptors 2 and 3 were expressed in SGC-7901 gastric cancer cell lines. Extracellular signal-regulated protein kinase and c-Fos protein level were decreased in gastric adenocarcinoma treated with octreotide. Moreover, fetal calf serum stimulated activator protein-1 binding activity could be suppressed by octreotide potentially.

Conclusion: Inhibition of sequential molecular events in MAPK pathway may interpret the mechanisms underlying the effect of octreotide on the growth of gastric adenocarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / pathology*
  • Animals
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Cell Division / drug effects
  • Cell Division / physiology
  • Humans
  • Mice
  • Mice, Nude
  • Mitogen-Activated Protein Kinases / metabolism*
  • Octreotide / pharmacology*
  • Stomach Neoplasms / pathology*

Substances

  • Antineoplastic Agents, Hormonal
  • Mitogen-Activated Protein Kinases
  • Octreotide