[Inhibition of activator protein-1 on the growth of gastric cancer by octreotide].

BACKGROUND & OBJECTIVE: Somatostatin is a multi-functional neuropeptide. Somatostatin and its analogues are able to inhibit the growth of neuroendocrine tumors and some gastrointestinal tumors. However, the effect of octreotide on growth of gastric carcinoma is still unknown. This study was designed to explore the mechanism of the effect of octreotide on growth of gastric cancer.

MATERIAL & METHODS: SGC-7901 cells were treated with octreotide at different concentrations for 24 hours. Proliferation of SGC-7901 cells was measured by 3H-thymidine incorporation assay. The nude mice bearing human stomach carcinoma were treated by octreotide for eight weeks. The c-Fos and extracellular signal-regulated protein kinase (ERK) protein expression levels were examined in SGC-7901 cells and carcinoma tissue by immunohistochemistry and immunoblotting. Activator protein-1 (AP-1) binding activity was detected by electrophoretic mobility shift assay (EMSA).

RESULTS

3H-thymidine incorporation into SGC-7901 cells was significantly decreased by octreotide and showed concentration-dependent. Octreotide could significantly inhibit the growth of orthotopical implanted gastric cancer, the inhibition rate for tumors was 62.3%. The c-Fos and ERK-1/ERK-2 proteins were decreased in the nude mice carcinoma tissues and SGC-7901 gastric carcinoma cells which treated with octreotide by immunohistochemistry or immunoblotting analysis. Moreover, the fetal calf serum (FCS) stimulated AP-1 binding activity on gastric cancer cell and the somatostatin analogue octreotide could inhibit this response efficiently.

CONCLUSION

Octreotide inhibits not only ERK-1/ERK-2 and c-Fos expressions but also AP-1 binding activity, which result in inhibition to proliferation of gastric carcinoma cell.