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研究Ｎａ＋／Ｈ＋交换泵（Ｎａ＋／Ｈ＋ｅｘｃｈａｎｇｅｒ，ＮＨＥ）基因家族第一亚型ＮＨＥ－１基因表达在肿瘤细胞内ｐＨ（ｐＨｉ）调节及凋亡调控中的作用。方法：在细胞培养中，以针对ＮＨＥ－１基因的硫代型反义核酸处理人肺腺癌Ａ５４９细胞，采用荧光标记法研究反义核酸对细胞的酸化效应；细胞凋亡原位检测法研究反义核酸诱导细胞凋亡。结果：Ａ５４９细胞酸化效应与ＮＨＥ－１反义核酸呈一定的剂量效应关系，当反义核酸浓度为２０μＭ时，可导致ｐＨｉ下降至６．５５，并诱发细胞凋亡，在处理时间为２４，４８，７２小时，其凋亡发生率分别为３０．１％，９１．２％，９９．６％。结论：①细胞酸化（ｐＨｉ下降至６．５５）能诱发人肺癌细胞凋亡；②人肺癌细胞ＮＨＥ－１基因表达能通过阻止其胞内酸化，对维持其抗凋亡生长性质具有重要作用
The role of NHE-1 gene expression in the Na+/H+ exchanger (NHE) gene family in the regulation of pH (pHi) and regulation of apoptosis in tumor cells was investigated. METHODS: Human lung adenocarcinoma cell line A549 was treated with thiol antisense nucleic acid against NHE-1 gene in cell culture. The effect of antisense nucleic acid on the acidification of cells was studied by fluorescence labeling; the in situ detection of apoptosis was studied. Antisense nucleic acids induce apoptosis. RESULTS: The acidification effect of A549 cells was dose-dependent with the NHE-1 antisense nucleic acid. When the antisense nucleic acid concentration was 20 μM, pHi decreased to 6.55 and induced apoptosis. The treatment time was 24, At 48, 72 hours, the incidence of apoptosis was 30.1%, 91.2%, and 99.6%, respectively. Conclusion: 1 Cell acidification (pHi down to 6.55) can induce apoptosis of human lung cancer cells; 2 lung cancer cell NHE-1 gene expression can play an important role in maintaining its anti-apoptotic growth properties by preventing its intracellular acidification.