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

Zhuo, Wenlei; Wang, Yan; Zhuo, Xianlu; Zhang, Yunsong; Ao, Xujun; Chen, Zhengtang

doi:10.1016/j.lungcan.2008.02.007

« Previous Next »Lung Cancer
Volume 62, Issue 1 , Pages 8-14, October 2008

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

Wenlei Zhuo
- Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
- These authors contributed equally to this work.
Yan Wang
- Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, China
- These authors contributed equally to this work.
- Corresponding author. Fax: +86 23 68753694.
Xianlu Zhuo
- Department of Otolaryngology, Southwest Hospital, Third Military Medical University, Chongqing, China
- These authors contributed equally to this work.
- The author works at Guiyang Medical College.
Yunsong Zhang
- Department of Cardiothoracic Surgery, Daping Hospital, Third Military Medical University, Chongqing, China
Xujun Ao
- Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Zhengtang Chen
- Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
- Corresponding author. Fax: +86 23 68753694.

Received 13 November 2007; received in revised form 5 February 2008; accepted 14 February 2008. published online 27 March 2008.

Summary

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.

Abbreviations: MAPKs, mitogen-activated protein kinases, JNK, c-Jun N-terminal kinase, NSCLC, non-small-cell lung cancer, EMT, epithelial-mesenchymal transition, TNFR, tumor necrosis factor receptors