Knockdown of creatine kinase B inhibits ovarian cancer progression by decreasing glycolysis

Int J Biochem Cell Biol. 2013 May;45(5):979-86. doi: 10.1016/j.biocel.2013.02.003. Epub 2013 Feb 14.


Creatine kinase plays a key role in the energy homeostasis of vertebrate cells. Creatine kinase B (CKB), a cytosolic isoform of creatine kinase, shows upregulated expression in a variety of cancers. In this research, we confirmed that some ovarian cancer tissues had elevated CKB expression at the protein level. The functions of CKB in ovarian cancer progression were investigated in the ovarian cancer cell line Skov3, which has a high CKB expression. It was found that CKB knockdown inhibited Skov3 cell proliferation and induced apoptosis under hypoxia or hypoglycemia conditions. CKB depletion also sensitized Skov3 to chemotherapeutic agents. Furthermore, the CKB knockdown reduced glucose consumption and lactate production, and increased ROS production and oxygen consumption. This suggested that CKB knockdown decreased cytosolic glycolysis and resulted in a tumor suppressive metabolic state in Skov3 cells. Consequently, we found that the knockdown of CKB induced G2 arrest in cell cycle by elevating p21 expression and affected the PI3K/Akt and AMPK pathways. These findings provide new insights in the role of CKB in cancer cell survival and tumor progression. Our results also suggest that CKB depletion/inhibition in combination with chemotherapeutic agents might have synergistic effects in ovarian cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology
  • Apoptosis
  • Cell Growth Processes / physiology
  • Cell Hypoxia / physiology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Creatine Kinase / biosynthesis
  • Creatine Kinase / deficiency*
  • Creatine Kinase / genetics
  • Creatine Kinase / metabolism
  • Disease Progression
  • Doxorubicin / pharmacology
  • Female
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • G2 Phase Cell Cycle Checkpoints / physiology
  • Gene Knockdown Techniques
  • Glycolysis
  • Humans
  • Isoenzymes
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Transfection
  • Up-Regulation


  • Antibiotics, Antineoplastic
  • Isoenzymes
  • Doxorubicin
  • Creatine Kinase