The anti-apoptotic livin gene is an important determinant for the apoptotic resistance of non-small cell lung cancer cells

Lung Cancer. 2006 Nov;54(2):135-42. doi: 10.1016/j.lungcan.2006.07.018. Epub 2006 Sep 11.


Cancer cells are typically characterized by increased resistance towards apoptosis. Livin (alternatively called ML-IAP or KIAP) is an anti-apoptotic protein which is expressed in several cancer forms. Using real-time reverse transcription-polymerase chain reaction (RT-PCR), we confirmed livin expression in a significant portion of non-small cell lung cancer (NSCLC) tissue samples and, in addition, detected livin expression in a number of NSCLC cell lines. In order to elucidate whether livin contributes to the apoptotic resistance of lung cancer cells, we silenced endogenous livin expression in a panel of cancer-derived NSCLC cell lines by RNA interference (RNAi). We observed that the targeted inhibition of livin strongly sensitized NSCLC cells to different pro-apoptotic stimuli, such as UV-irradiation or the chemotherapeutic drug etoposide. In addition, long-term silencing of livin blocked the outgrowth of NSCLC cells in colony formation assays. These effects of small interfering (si)RNA were specific for livin-expressing tumor cells. Our results indicate that Livin is an important contributor to the apoptosis resistance of NSCLC cells and may serve as a novel molecular target for therapeutic inhibition in NSCLC.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / physiology*
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Apoptosis / radiation effects
  • Carcinoma, Non-Small-Cell Lung / physiopathology*
  • Cell Line, Tumor
  • Etoposide / pharmacology
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / physiology*
  • Lung Neoplasms / physiopathology*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • RNA Interference
  • RNA, Small Interfering
  • Transfection
  • Tumor Stem Cell Assay
  • Ultraviolet Rays


  • Adaptor Proteins, Signal Transducing
  • BIRC7 protein, human
  • Inhibitor of Apoptosis Proteins
  • Neoplasm Proteins
  • RNA, Small Interfering
  • Etoposide