Suppression of ClC-3 channel expression reduces migration of nasopharyngeal carcinoma cells.

Abstract

Recent studies suggest that chloride (Cl-) channels regulate tumor cell migration. In this report, we have used antisense oligonucleotides specific for ClC-3, the most likely molecular candidate for the volume-activated Cl- channel, to investigate the role of ClC-3 in the migration of nasopharyngeal carcinoma cells (CNE-2Z) in vitro. We found that suppression of ClC-3 expression inhibited the migration of CNE-2Z cells in a concentration-dependent manner. Whole-cell patch-clamp recordings and image analysis further demonstrated that ClC-3 suppression inhibited the volume-activated Cl- current (I(Cl,vol)) and regulatory volume decrease (RVD) of CNE-2Z cells. The expression of ClC-3 positively correlated with cell migration, I(Cl,vol) and RVD. These results strongly suggest that ClC-3 is a component or regulator of the volume-activated Cl- channel. ClC-3 may regulate CNE-2Z cell migration by modulating cell volume. ClC-3 may be a new target for cancer therapies.

• Authors: Jianwen Mao, Lixin Chen, Bin Xu, Lijing Wang, Hongzhi Li, Jiao Guo, Weidong Li, Sihuai Nie, Tim J C Jacob, Liwei Wang
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 75 Issue 9 Pg. 1706-16 (May 01 2008) ISSN: 1873-2968 [Electronic] England
• PMID: 18359479 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chloride Channels
• Chlorides
• ClC-3 channel
• Oligonucleotides, Antisense

Topics

• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Size (drug effects)
• Chloride Channels (antagonists & inhibitors, biosynthesis, genetics)
• Chlorides (metabolism)
• Dose-Response Relationship, Drug
• Humans
• Inhibitory Concentration 50
• Nasopharyngeal Neoplasms (metabolism, pathology)
• Oligonucleotides, Antisense (pharmacology)
• Patch-Clamp Techniques
• Transfection