title: Functional expression of chloride channels and their roles in the cell cycle and cell proliferation in highly differentiated nasopharyngeal carcinoma cells.
abstract: We previously demonstrated that the growth of the poorly differentiated nasopharyngeal carcinoma cells (CNE-2Z) was more dependent on the activities of volume-activated chloride channels than that of the normal nasopharyngeal epithelial cells (NP69-SV40T). However, the activities and roles of such volume-activated chloride channels in highly differentiated nasopharyngeal carcinoma cells (CNE-1) are not clarified. In this study, it was found that a volume-activated chloride current and a regulatory volume decrease (RVD) were induced by 47% hypotonic challenges. The current density and the capacity of RVD in the highly differentiated CNE-1 cells were lower than those in the poorly differentiated CNE-2Z cells, and higher than those in the normal cells (NP69-SV40T). The chloride channel blockers, 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and tamoxifen inhibited the current and RVD. Depletion of intracellular Cl(-) abolished the RVD. The chloride channel blockers reversibly inhibited cell proliferation in a concentration- and time-dependent manner, and arrested cells at the G0/G1 phases, but did not change cell viability. The sensitivity of the three cell lines to the chloride channel blockers was different, with the highest in poorly differentiated cells (CNE-2Z) and the lowest in the normal cells (NP69-SV40T). ClC-3 proteins were expressed in the three cells and distributed inside the cells as well as on the cell membrane. In conclusion, the highly differentiated nasopharyngeal carcinoma CNE-1 cells functionally expressed the volume-activated chloride channels, which may play important roles in controlling cell proliferation through modulating the cell cycle, and may be associated with cell differentiation. Chloride channels may be a potential target of anticancer therapy.
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Weiyuan
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Linyan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Shanwen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Lianshun
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Ruiling
authors.initials: R
authors.lastname: Lu
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
keywords: Cell cycle; cell proliferation; chloride channels; nasopharyngeal carcinoma; regulatory volume decrease