双甲基氨氯吡咪抑制人肺癌细胞株Na^+/H^+交换泵-1活性诱导肿瘤细胞酸化和凋亡  

Induction of the acidification and apoptosis of human lung cancer cell line through inhibition of Na +/H + exchanger 1 with dimethyl amiloride

作　　者：吴国明[1,2] 历为良[1,2] 黄桂君[1,2] 钱桂生 

机构地区：[1]第三军医大学附属新桥医院呼吸内科研究所 [2]解放军412医院呼吸内科

出　　处：《第三军医大学学报》1998年第6期476-479,共4页Journal of Third Military Medical University

基　　金：第三军医大学科研基金

摘　　要：目的：研究Ｎａ＋／Ｈ＋交换泵－１（ＮＨＥ－１）在肺癌细胞增殖／凋亡调控中的作用。方法：采用荧光探针法检则ＮＨＥ－１抑制剂双甲基氨氯吡咪（ＤＭＡ）对人肺巨细胞癌高转移株（ＰＬＡ－８０１Ｄ）细胞的酸化作用；以活细胞计数法检测ＤＭＡ对ＰＬＡ－８０１Ｄ细胞增殖生长的抑制作用；采用原位细胞凋亡检测法观察ＤＭＡ诱导ＰＬＡ－８０１Ｄ细胞的凋亡。结果：经２５μｍｏｌ／Ｌ以上ＤＭＡ处理２４ｈ或５０μｍｏｌ／Ｌ处理８ｈ以上即能酸化ＰＬＡ－８０１Ｄ细胞，其细胞内ｐＨ（ｐＨｉ）显著降低，并诱导了ＰＬＡ－８０１Ｄ细胞的凋亡，肿瘤细胞的增殖生长也显著受抑。结论：ＮＨＥ－１在肺癌细胞增殖／凋亡调控中起重要作用。Objective: To study the role of Na +/H + exchanger 1 (NHE 1) in modulation of proliferation/apoptosis of lung cancer cells. Methods: The acidification, inhibition and apoptosis of human lung cancer cell line PLA 801D induced by dimethyl amiloride (DMA), one of the NHE 1 inhibitors, was determined with BCECF, a fluorescent probe, living cell count and in situ tailing respectively. Results: There was obvious acidification of PLA 801D cells incubated with DMA at a volume more than 25 μmol/L for 24 h or 50 μmol/L for 8h and the intracellular pH (pHi) of the tumor cells declined significantly ( P <0.05 0.01). Meanwhile, apoptosis of PLA 801D cells was induced and proliferation of them markedly inhibited. Conclusion: NHE 1 may play an important role in modulation of proliferation/apoptosis of lung cancer cells and inhibition of the enhanced NHE 1 activity of the tumor cells may be an anticancer strategy.

关 键 词：NHE-1 细胞酸化 细胞凋亡 肺肿瘤 DMA 

分 类 号：R734.202[医药卫生—肿瘤]