Knockdown of Snail, a novel zinc finger transcription factor, via RNA interference increases A549 cell sensitivity to cisplatin via JNK/mitochondrial pathway

Lung Cancer. 2008 Oct;62(1):8-14. doi: 10.1016/j.lungcan.2008.02.007. Epub 2008 Mar 26.


Previous reports have implicated epithelial-mesenchymal transition (EMT) as a major cause of cancer. Snail, a novel zinc finger transcription factor, was suggested to be an important inducer of EMT and therefore be involved in different phases of tumorigenicity. However, whether Snail could increase chemoresistance of cancer cells to chemotherapeutic agent remains unclear. To evaluate the roles and possible mechanisms of Snail in chemoresistance of lung cancer cells to cisplatin, we utilized RNA interference to knockdown Snail expression in A549 cells and further assessed the cell viability and apoptosis as well as possible signaling transduction pathways. The data showed that Snail depletion sensitized A549 cells to cisplatin possibly by inducing activation of JNK/mitochondrial pathway, suggesting critical roles of Snail in A549 cell chemoresistance to cisplatin and raising the possibility of Snail depletion as a promising approach to lung cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Survival
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics*
  • Humans
  • In Situ Nick-End Labeling
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • MAP Kinase Kinase 4 / metabolism*
  • Mitochondria / metabolism
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / physiology
  • Snail Family Transcription Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Antineoplastic Agents
  • Snail Family Transcription Factors
  • Transcription Factors
  • MAP Kinase Kinase 4
  • Cisplatin