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Published on: July 17, 2018
ClC-3 chloride channels are essential for cell proliferation and cell cycle progression in nasopharyngeal carcinoma
Bin Xu1, Jianwen Mao, Liwei Wang
1Guangdong Pharmaceutical University, Guangzhou, China.
Abstract:
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.
Insights
ClC-3 protein expression drives nasopharyngeal carcinoma cell proliferation and cell cycle progression. Inhibiting ClC-3 with antisense oligonucleotides reduced tumor cell growth and volume-activated chloride currents, suggesting ClC-3 as a potential cancer therapeutic target.
Area of Science:
- Molecular Biology
- Oncology
- Physiology
Background:
- ClC-3, a gene encoding a protein for volume-activated chloride channels, is implicated in tumor development.
- Understanding ClC-3's role in cell proliferation is crucial for cancer research.
Purpose of the Study:
- To investigate the mechanism by which ClC-3 affects cell proliferation in nasopharyngeal carcinoma CNE-2Z cells.
- To determine if ClC-3 is a viable therapeutic target for human cancers.
Main Methods:
- Utilized an antisense oligonucleotide "knock-down" strategy to inhibit ClC-3 expression.
- Employed immunoblots and MTT assays to assess protein expression and cell proliferation.
- Analyzed cell cycle progression, cloning efficiency, and volume-activated chloride currents (I(Cl,vol)) and regulatory volume decrease (RVD).
Main Results:
- ClC-3 expression was cell cycle dependent and correlated with cell proliferation.
- ClC-3 antisense oligonucleotide inhibited ClC-3 protein expression, cell proliferation, cloning efficiency, and induced S-phase arrest.
- Inhibition of ClC-3 reduced I(Cl,vol) and RVD in a concentration-dependent manner, correlating positively with cell proliferation.
Conclusions:
- ClC-3 plays a significant role in cell proliferation and cell cycle progression.
- ClC-3 modulates I(Cl,vol) and RVD, impacting cancer cell growth.
- ClC-3 represents a potential therapeutic target for human cancers, particularly nasopharyngeal carcinoma.
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