Functional expression of chloride channels and their roles in the cell cycle and cell proliferation in highly differentiated nasopharyngeal carcinoma cells.
Functional expression of chloride channels and their roles in the cell cycle and cell proliferation in highly differentiated nasopharyngeal carcinoma cells.
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高分化鼻咽癌细胞氯离子通道的功能表达及其在细胞周期和细胞增殖中的作用
DOI：
10.14814/phy2.12137
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发表时间：
2014-09-01
影响因子：
2.5
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Huang W;Liu M;Zhu L;Liu S;Luo H;Ma L;Wang H;Lu R;Sun X;Chen L;Wang L
我们之前已经证明，低分化鼻咽癌细胞（CNE‐2Z）的生长比正常鼻咽癌上皮细胞（NP69‐SV40T）更依赖于体积激活的氯离子通道的活性。然而，这种体积激活的氯离子通道在高分化鼻咽癌细胞（CNE‐1）中的活性和作用尚不清楚。在这项研究中，我们发现47%的低渗刺激诱导了一个体积激活的氯离子电流和一个调节体积减少（RVD）。高分化CNE‐1细胞的电流密度和RVD容量低于低分化CNE‐2Z细胞，高于正常细胞（NP69‐SV40T）。氯离子通道阻滞剂、5‐硝基‐2‐（3‐苯基丙基氨基）苯甲酸（NPPB）和他莫昔芬抑制电流和RVD。细胞内Cl−的消耗使RVD消失。氯离子通道阻滞剂以浓度和时间依赖性的方式可逆地抑制细胞增殖，并在G0/G1期阻滞细胞，但不改变细胞活力。三种细胞系对氯离子通道阻滞剂的敏感性不同，低分化细胞（CNE‐2Z）的敏感性最高，正常细胞（NP69‐SV40T）的敏感性最低。ClC‐3蛋白在这三个细胞中表达，并分布在细胞内和细胞膜上。综上所述，高分化鼻咽癌CNE‐1细胞功能表达了体积激活的氯离子通道，该通道可能通过调节细胞周期在控制细胞增殖中发挥重要作用，并可能与细胞分化有关。氯离子通道可能是抗癌治疗的潜在靶点。在本文中，我们证明了体积激活的氯离子通道参与调节CNE - 1细胞增殖和细胞周期进程。因此，体积激活的氯离子通道可能是抗癌治疗的潜在靶点。
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. In this paper, we demonstrated that the volume‐activated chloride channels were involved in regulating CNE‐1 cells proliferation and cell cycle progress. Thus, volume‐activated chloride channels may be a potential target of anticancer therapy.