Short interfering RNA directed against TWIST, a novel zinc finger transcription factor, increases A549 cell sensitivity to cisplatin via MAPK/mitochondrial pathway

Biochem Biophys Res Commun. 2008 May 16;369(4):1098-102. doi: 10.1016/j.bbrc.2008.02.143. Epub 2008 Mar 10.


Previous reports have implicated epithelial-mesenchymal transition (EMT) as a major cause of cancer. TWIST, 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 TWIST suppression could increase chemosensitivity of cancer cells to chemotherapeutic agent remains unclear. In the present study, we utilized RNA interference to knockdown TWIST expression in A549 cells and further assessed the cell viability and apoptosis as well as possible MAPKs and mitochondrial pathways. The data showed that TWIST depletion significantly sensitized A549 cells to cisplatin by inducing activation of JNK/mitochondrial pathway but not ERK and p-38 pathways, suggesting critical roles of TWIST in A549 cell chemoresistance to cisplatin and raising the possibility of TWIST depletion as a promising approach to lung cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm / genetics
  • Genetic Vectors
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / metabolism*
  • MAP Kinase Signaling System
  • Mitochondria / enzymology
  • Nuclear Proteins / antagonists & inhibitors*
  • Nuclear Proteins / genetics
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Twist-Related Protein 1 / antagonists & inhibitors*
  • Twist-Related Protein 1 / genetics
  • Zinc Fingers


  • Antineoplastic Agents
  • Nuclear Proteins
  • RNA, Small Interfering
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • JNK Mitogen-Activated Protein Kinases
  • Cisplatin