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Somatostatin analog inhibits the growth of insulinoma cells by p27-mediated G1 cell cycle arrest.

AbstractOBJECTIVES:
Although the somatostatin analog octreotide (OCT) has been used for uncontrollable insulinoma, the mechanism involved is still unknown. The aim of this study was to elucidate the therapeutic effect of OCT for insulinoma.
METHODS:
Mouse insulinoma cell line MIN6 cells were cultured with OCT to clarify its antiproliferative effects, the expression of somatostatin receptor subtypes, cell cycle, p27 expression, and cdc2 kinase activity. The changes of the messenger RNA expression profiles were examined by microarray analysis. Intraperitoneal OCT treatment was given to insulinoma model IT6 mice for 4 weeks.
RESULTS:
MIN6 cells expressed somatostatin receptor 2A, 3, and 5 under the OCT treatment. Octreotide showed a dose-dependent antiproliferative effect on MIN6 cells but not on the other cell lines. p27 expression and cdc2 kinase activity in MIN6 cells became prominent with OCT treatment. At the messenger RNA level, several molecules in the mitogen-activated protein kinase signaling pathway were downregulated. The sizes of the individual tumors tended to be smaller in the OCT-treated group. p27 expression was seen in the tumor tissue, but no apoptotic marker was detected.
CONCLUSION:
Octreotide acted through a cytostatic mechanism and could be an effective therapy for insulinoma.
AuthorsTakeshi Aoki, Fuyuhiko Motoi, Naoaki Sakata, Takeshi Naitoh, Yu Katayose, Shinichi Egawa, Jun-ichi Miyazaki, Michiaki Unno
JournalPancreas (Pancreas) Vol. 43 Issue 5 Pg. 720-9 (Jul 2014) ISSN: 1536-4828 [Electronic] United States
PMID24694834 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents, Hormonal
  • Receptors, Somatostatin
  • Cyclin-Dependent Kinase Inhibitor p27
  • CDC2 Protein Kinase
  • Octreotide
Topics
  • Aged
  • Animals
  • Antineoplastic Agents, Hormonal (administration & dosage, pharmacology, therapeutic use)
  • Blotting, Western
  • CDC2 Protein Kinase (genetics, metabolism)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Cyclin-Dependent Kinase Inhibitor p27 (genetics, metabolism)
  • Dose-Response Relationship, Drug
  • Female
  • G1 Phase Cell Cycle Checkpoints (genetics)
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Humans
  • Immunohistochemistry
  • Injections, Intraperitoneal
  • Insulinoma (drug therapy, genetics, pathology)
  • Liver (drug effects, pathology, surgery)
  • Mice
  • NIH 3T3 Cells
  • Octreotide (administration & dosage, pharmacology, therapeutic use)
  • Pancreatic Neoplasms (drug therapy, genetics, pathology)
  • Receptors, Somatostatin (genetics, metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcriptome (drug effects)
  • Treatment Outcome

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