XIAP-mediated protection of H460 lung cancer cells against cisplatin

Eur J Pharmacol. 2010 Feb 10;627(1-3):75-84. doi: 10.1016/j.ejphar.2009.11.003. Epub 2009 Nov 10.

Abstract

Molecular mechanism(s) responsible for drug resistance of non-small cell lung cancer (NSCLC) cells to cisplatin was investigated. Results showed that cisplatin (50muM)-induced cell death (apoptosis) was more significant in CH27 and A549 cell lines than in H460. The high protein levels of X-linked inhibitor-of-apoptosis protein (XIAP) observed in H460 cells appeared to play a key role in the regulation of cisplatin resistance of H460 cells. XIAP can bind to and suppress the activities of caspase 3 in H460 cells and lead to apoptosis inhibition of these cells. Blockade of XIAP activity by Embelin (XIAP inhibitor) or siRNA has increased caspase 3 activities and promoted cisplatin-induced cell death of H460 cells. The results indicate a therapeutic value of Embelin and/or XIAP siRNA in the control of cisplatin-resistant NSCLC cells (H460).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Benzoquinones / pharmacology
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Cytochromes c / metabolism
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm / drug effects
  • Gene Knockdown Techniques
  • Humans
  • Lung Neoplasms / pathology*
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • RNA, Small Interfering / genetics
  • Time Factors
  • X-Linked Inhibitor of Apoptosis Protein / antagonists & inhibitors
  • X-Linked Inhibitor of Apoptosis Protein / deficiency
  • X-Linked Inhibitor of Apoptosis Protein / genetics
  • X-Linked Inhibitor of Apoptosis Protein / metabolism*

Substances

  • Benzoquinones
  • RNA, Small Interfering
  • X-Linked Inhibitor of Apoptosis Protein
  • Cytochromes c
  • Caspase 3
  • Cisplatin
  • embelin