Glycogen synthase kinase-3beta positively regulates the proliferation of human ovarian cancer cells

Cell Res. 2006 Jul;16(7):671-7. doi: 10.1038/


Although glycogen synthase kinase-3 (GSK-3) might act as a tumor suppressor since its inhibition is expected to mimic the activation of Wnt-signaling pathway, GSK-3beta may contribute to NF-kappaB activation in cancer cells leading to increased cancer cell proliferation and survival. Here we report that GSK-3beta activity was involved in the proliferation of human ovarian cancer cell both in vitro and in vivo. Inhibition of GSK-3 activity by pharmacological inhibitors suppressed proliferation of the ovarian cancer cells. Overexpressing constitutively active form of GSK-3beta induced entry into the S phase, increased cyclin D1 expression and facilitated the proliferation of ovarian cancer cells. Furthermore, GSK-3 inhibition prevented the formation of the tumor in nude mice generated by the inoculation of human ovarian cancer cells. Our findings thus suggest that GSK-3beta activity is important for the proliferation of ovarian cancer cells, implicating this kinase as a potential therapeutic target in ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / physiology
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cyclin D1 / metabolism
  • Enzyme Inhibitors / metabolism
  • Female
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Lithium Chloride / metabolism
  • Mice
  • Ovarian Neoplasms / metabolism*


  • Enzyme Inhibitors
  • Cyclin D1
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Glycogen Synthase Kinase 3
  • Lithium Chloride