Octreotide Stimulates Somatostatin Receptor-Induced Apoptosis of SW480 Colon Cancer Cells by Activation of Glycogen Synthase Kinase-3 beta, A Wnt/beta-Catenin Pathway Modulator

Background/Aims: Peptide hormone somatostatin and its receptors (SSTRs) have a wide range of physiological functions and play a role in the treatment of numerous human diseases, including colorectal cancer. Octreotide, a somatostatin-analog peptide, inhibits growth of colonic cancer SW480 cells through Wnt/beta-catenin pathway modulation. However, the specific octreotide-stimulating SSTR subtypes and the signal-transduction mechanism responsible for the negative regulation of Wnt/beta-catenin pathway by octreotide have not been fully elucidated. Methodology: Octreotide-induced apoptosis in SW480 colon cancer cells mediated by SSTR2,SSTR5-dependent regulation of the Wnt/beta-catenin pathway components GSK-3 beta and beta-catenin was investigated. Cell apoptosis of SW480 cells was measured by apoptosis-DNA ladder assay. SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5 mRNA expression levels were confirmed by RTPCR; beta-catenin, TCF-4, cyclin D1, c-Myc, and GSK-3 beta protein levels were examined by Western blot. The distribution of beta-catenin in the cell was analyzed with immunocytochemistry. Results: Octreotide treatment increased SSTR2,SSTR5-induced apoptosis of SW480 colon cancer cells, promoted the plasma membrane accumulation of beta-catenin, inactivated T-cell factor-dependent transcription, and downregulated Wnt target genes cyclin D1 and c-Myc. Further, octreotide treatment mediated the activation of GSK-3. Conclusions: These preliminary findings showed the negative regulation of the Wnt/beta-catenin pathway by peptide hormone G protein-coupled receptors SSTRs.