Octreotide surpress gastric cancer growth through inhibition of MAPK pathway
Objectives: 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 the probable mechanisms behind the effects. Methods: Proliferation of gastric cancer cell line affected with octreotide was determined by 3H-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. Extrcellular 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: 3H-thymidine incorporation into SGC-7901 cells was significantly decreased by octreotide in a manner of concentration dependence. 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 receptor 2 and 3 were expressed in SGC-7901 gastric cancer cell lines. Extracellular signal-regulated protein kinase and the c-Fos protein level were decreased in gastric adenocarcinoma treated with octreotide. Moreover, the fetal calf serum stimulated activator protein-1 binding activity could be suppressed by octreotide potentially. Conclusions: Inhibition of sequential molecular events in MAPK pathway may interpret the mechanisms behind the suppressive effect of octreotide on the growth of gastric adenocarcinoma.
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