Role of X-linked inhibitor of apoptosis protein in chemoresistance in ovarian cancer: possible involvement of the phosphoinositide-3 kinase/Akt pathway

Drug Resist Updat. Jul-Aug 2002;5(3-4):131-46. doi: 10.1016/s1368-7646(02)00003-1.

Abstract

Although cisplatin derivatives are first-line chemotherapeutic agents for the treatment of epithelial ovarian cancer, chemoresistance remains a major hurdle to successful therapy and the molecular mechanisms involved are poorly understood. Apoptosis is the cellular underpinning of cisplatin-induced cell death, which is associated with expression of specific "death" genes and down-regulation of "survival" counterparts. The X-linked inhibitor of apoptosis proteins (Xiap), an intracellular anti-apoptotic protein, plays a key role in cell survival by modulating death signaling pathways and is a determinant of cisplatin resistance in ovarian cancer cells in vitro. This review focuses on the role of Xiap and its interactions with the phosphoinositide-3 kinase (PI3K)/Akt cell survival pathway in conferring resistance of ovarian cancer cells to chemotherapeutic agents and discusses potential therapeutic strategies in overcoming chemoresistant ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Cisplatin / therapeutic use*
  • Drug Resistance, Neoplasm / physiology*
  • Female
  • Humans
  • Ovarian Neoplasms / drug therapy*
  • Phosphatidylinositol 3-Kinases / physiology*
  • Protein-Serine-Threonine Kinases*
  • Proteins / physiology
  • Proteins / therapeutic use*
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-akt
  • X-Linked Inhibitor of Apoptosis Protein

Substances

  • Proteins
  • Proto-Oncogene Proteins
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • Phosphatidylinositol 3-Kinases
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Cisplatin