title: Octreotide stimulates somatostatin receptor-induced apoptosis of SW480 colon cancer cells by activation of glycogen synthase kinase-3β, A Wnt/β-catenin pathway modulator.
abstract: OBJECTIVE
  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/β-catenin pathway modulation. However, the specific octreotide-stimulating SSTR subtypes and the signal-transduction mechanism responsible for the negative regulation of Wnt/β-catenin pathway by octreotide have not been fully elucidated.
  
  
  METHODS
  Octreotide-induced apoptosis in SW480 colon cancer cells mediated by SSTR2,SSTR5-dependent regulation of the Wnt/β-catenin pathway components GSK-3β and β-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 RT-PCR; β-catenin, TCF-4, cyclin D1, c-Myc, and GSK-3β protein levels were examined by Western blot. The distribution of β-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 β-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/β-catenin pathway by peptide hormone G protein-coupled receptors SSTRs.
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Bao
authors.forename: Qing-Mo
authors.initials: QM
authors.lastname: Liang
authors.forename: Jian-Wu
authors.initials: JW
authors.lastname: Long
authors.forename: Zhong-Sheng
authors.initials: ZS
authors.lastname: Xiao
authors.forename: Zhong-Jun
authors.initials: ZJ
authors.lastname: Jiang
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Zhi-Xiang
authors.initials: ZX
authors.lastname: Long
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D015282:Octreotide / Q000494:pharmacology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D051820:TCF Transcription Factors / Q000378:metabolism; D013997:Time Factors; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D018931:Antineoplastic Agents, Hormonal; C495270:CTNNB1 protein, human; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C574734:SSTR2 protein, human; D051820:TCF Transcription Factors; D051176:beta Catenin; C094573:somatostatin receptor 5; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D015282:Octreotide