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氯通道在鼻咽癌细胞凋亡性细胞容积减小和细胞凋亡中的作用

潘廷才1,杨林杰1,2,朱林燕1,2,陈丽新1,2,王立伟1,2   

  1. 1. 暨南大学医学院
    2.
  • 收稿日期:2010-11-26 修回日期:2011-03-07 出版日期:2011-06-15 发布日期:2011-06-15
  • 通讯作者: 潘廷才

Inhibition of cell apoptotic volume decrease and apoptosis by blocking Cl- channels in nasopharyngeal carcinoma cells

  • Received:2010-11-26 Revised:2011-03-07 Published:2011-06-15 Online:2011-06-15
  • Contact: Ting-Cai PAN

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摘要： 摘 要 目的：探讨氯通道在抗肿瘤药物5-氟尿嘧啶（5-Fluorouracil, 5-Fu）诱导的低分化鼻咽癌细胞（CNE-2Z）凋亡性细胞容积减小（Apoptotic Volume Decrease, AVD）和细胞凋亡中的作用。方法：实验采用活细胞影像系统实时拍摄细胞图像，检测细胞容积变化，Hoechst染色在荧光显微镜下观察细胞凋亡并计算细胞凋亡率。结果： 5-Fu（100?mol/L）诱导CNE-2Z细胞凋亡性细胞容积减小， 5-Fu处理细胞120min时细胞容积减少至加药前对照值的88.2%。 5-Fu作用48h诱导CNE-2Z细胞凋亡率为49.2 ％。氯通道阻断剂5-硝基-2-(3-苯丙胺)苯甲酸（5-nitro-2-(3-henylpropylamino) benzoic acid，NPPB）明显抑制5-Fu诱导的细胞凋亡性细胞容积减小和细胞凋亡,抑制率分别为79.1％和 74.9%。结论：抑制氯通道显著拮抗5-Fu诱导的凋亡性细胞容积减小和细胞凋亡，提示5-Fu可能通过激活氯通道和诱导AVD而使细胞凋亡，氯通道的激活在5-Fu抗肿瘤机制中起重要作用。

关键词: 5-氟尿嘧啶, 鼻咽肿瘤, 氯通道, 凋亡性细胞容积减小, 凋亡

Abstract: Abstract Objective: To investigate the roles of chloride channels in apoptotic volume decrease (AVD) and apoptosis in nasopharyngeal carcinoma cells (CNE-2Z). Methods: The changes of cell volume were monitored and analyzed by the time-lapse imaging technique. Cell apoptotic rates were measured by using nuclear staining analysis by Hoechst 33258. Results：The results showed that 5-Fu (100?mol/L) induced an early cell volume decrease just in a few minutes. The cell volume was decreased to 88.2% of the control volume in 120 min. The apoptotic rate induced by 5-Fu was 49.2% 48 h after treatments. Chloride channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) prevented appearance of 5-Fu-induced cell shrinkage and apoptosis by 79.1% and 74.9%, respectively. Conclusion: Chloride channel blockers could inhibit 5-Fu-induced apoptotic cell volume decrease and apoptosis. The results suggest that chloride channels may contribute to 5-Fu-induced apoptosis by activation of chloride channels and inducing apoptotic volume decrease in CNE-2Z cells. The activation of chloride channels play an important role in the anti-tumour action of 5-Fu.

Key words: 5-Fluorouracil, nasopharyngeal neoplasms, apoptotic volume decrease, chloride channel, apoptosis