ShRNA silencing glycogen synthase kinase-3 beta inhibits tumor growth and angiogenesis in pancreatic cancer

Cancer Lett. 2012 Mar 28;316(2):178-86. doi: 10.1016/j.canlet.2011.10.033. Epub 2011 Nov 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinoma, Pancreatic Ductal / blood supply
  • Carcinoma, Pancreatic Ductal / enzymology
  • Carcinoma, Pancreatic Ductal / pathology
  • Carcinoma, Pancreatic Ductal / therapy*
  • Cell Differentiation / physiology
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Female
  • Gene Knockdown Techniques
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Glycogen Synthase Kinase 3 / biosynthesis
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neovascularization, Pathologic / enzymology
  • Pancreatic Neoplasms / blood supply
  • Pancreatic Neoplasms / enzymology
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy*
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics
  • Xenograft Model Antitumor Assays

Substances

  • RNA, Small Interfering
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Glycogen Synthase Kinase 3