ClC-3 chloride channels are essential for cell proliferation and cell cycle progression in nasopharyngeal carcinoma cells

Abstract

<title>Abstract</title> ClC-3, a gene encoding a candidate protein for volume-activated chloride (Cl⁻) 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 Cl⁻ current (<italic>I</italic>_Cl,vol) and the regulatory volume decrease (RVD) in a concentration-dependent manner. Additionally, the <italic>I</italic>_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 <italic>I</italic>_Cl,vol and RVD. CIC-3 may represent a therapeutic target in human cancer.