ClC-3 chloride channels are essential for cell proliferation and cell cycle progression in nasopharyngeal carcinoma cells.
ClC-3, a gene encoding a candidate protein for volume-activated chloride (C(-)) channels, may be involved in tumor development. Herein we report a study using an antisense "knock-down" strategy to investigate the mechanism by which ClC-3 affects cell proliferation in nasopharyngeal carcinoma CNE-2Z cells. With immunoblots and MTT assays we demonstrated that the expression of ClC-3 was cell cycle dependent and in a similar concentration-dependent manner, an antisense oligonucleotide specific for ClC-3 inhibited ClC-3 protein expression and cell proliferation. The expression level of ClC-3 correlated with cell proliferation. Moreover, in the cells exposed to a ClC-3 antisense oligonucleotide, the cloning efficiency was inhibited, and cells were arrested in the S phase. The ClC-3 antisense oligonucleotide inhibited the volume-activated C(-) current (I(Cl,vol)) and the regulatory volume decrease (RVD) in a concentration-dependent manner. Additionally, the I(Cl,vol) or RVD was positively correlated with cell proliferation in the treated cells. In conclusion, ClC-3 is involved in cell proliferation and cell cycle progression through a mechanism involving modulation of I(Cl,vol) and RVD. CIC-3 may represent a therapeutic target in human cancer.
Xu
Bin
B
Guangdong Pharmaceutical University, Guangzhou, China.
Mao
Jianwen
J
Wang
Liwei
L
Zhu
Linyan
L
Li
Hongzhi
H
Wang
Weizhang
W
Jin
Xiaobao
X
Zhu
Jiayong
J
Chen
Lixin
L
D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048429:Cell Size; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D002712:Chlorides / Q000502:physiology; D006801:Humans; D008297:Male; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016376:Oligonucleotides, Antisense; D018408:Patch-Clamp Techniques
D018118:Chloride Channels; D002712:Chlorides; C115376:ClC-3 channel; D016376:Oligonucleotides, Antisense