Abstract
Glycogen synthase kinase-3 beta (GSK-3β), a serine/threonine protein kinase, plays a vital role in the tumorigenesis of many cancers, but its role in pancreatic cancer remains unknown. In this study, we showed that GSK-3β was aberrantly activated in pancreatic cancer. GSK-3β knockdown resulted in arrested proliferation and increased apoptosis in pancreatic cancer cell lines. Expression of Bcl-2 and vascular endothelial growth factor (VEGF) decreased significantly in a GSK-3β knockdown group. In a xenograft tumor model, GSK-3β knockdown inhibited tumor growth and angiogenesis. Our study showed that GSK-3β may become a promising therapeutic target for human pancreatic cancer.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / genetics
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Carcinoma, Pancreatic Ductal / blood supply
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Carcinoma, Pancreatic Ductal / enzymology
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Carcinoma, Pancreatic Ductal / pathology
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Carcinoma, Pancreatic Ductal / therapy*
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Cell Differentiation / physiology
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Cell Growth Processes / genetics
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Cell Line, Tumor
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Female
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Gene Knockdown Techniques
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Glycogen Synthase Kinase 3 / antagonists & inhibitors*
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Glycogen Synthase Kinase 3 / biosynthesis
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Glycogen Synthase Kinase 3 / genetics
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 beta
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Humans
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Male
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Mice
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Mice, Nude
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Middle Aged
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Neovascularization, Pathologic / enzymology
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Pancreatic Neoplasms / blood supply
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Pancreatic Neoplasms / enzymology
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Pancreatic Neoplasms / pathology
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Pancreatic Neoplasms / therapy*
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RNA, Small Interfering / administration & dosage*
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RNA, Small Interfering / genetics
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Xenograft Model Antitumor Assays
Substances
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RNA, Small Interfering
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GSK3B protein, human
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Glycogen Synthase Kinase 3 beta
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Gsk3b protein, mouse
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Glycogen Synthase Kinase 3