Takeshi Aoki1, Fuyuhiko Motoi, Naoaki Sakata, Takeshi Naitoh, Yu Katayose, Shinichi Egawa, Jun-ichi Miyazaki, Michiaki Unno. 1. From the Divisions of *Hepato-Biliary-Pancreatic Surgery, and †Integrated Surgery and Oncology, Department of Surgery, Tohoku University Graduate School of Medicine, Aobaku, Sendai, Japan; ‡Division of International Cooperation for Disaster Medicine, International Research Institute of Disaster Science, Tohoku University, Aobaku, Sendai, Japan; and §Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Abstract
OBJECTIVES: 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.
OBJECTIVES: 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:Mouseinsulinoma 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.