Influence of Microenvironment pH Value on Growth of Tumor Cells
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摘要: 目的 观察肿瘤细胞外pH值(pHe)对于肿瘤细胞活力和生物学行为的影响。方法 以人大肠癌株SW116、LoVo细胞及人胃癌细胞株MKN-28为研究对象,采用MTT法比较细胞在不同微环境pH 值下细胞活力的变化,并观察细胞形态的变化,测定细胞在不同pH值下的凋亡率。采用实时荧光定量PCR测定不同pH值下Bcl-2及survivin基因表达的变化。结果 当培养液pH值从7.4下降到6.8后,三株细胞的活力均有明显增加(P<0.05)。形态观察发现,在pHe 6.8时,细胞在培养液的密度更高,形态较pHe7.4时无明显变化。凋亡检测显示,pHe6.8时细胞活力良好,未发生凋亡。在pHe6.8环境下,细胞Bcl-2基因表达较pHe7.4时显著降低(P<0.05),survivin基因表达的变化差异无统计学意义。结论 肿瘤局部微环境的低pH值使肿瘤细胞加速生长,细胞活力及形态无变化,细胞凋亡相关基因Bcl-2的表达亦受到影响。Abstract: Objective To explore the influence of extracellular pH(pHe) on the growth and biological behavior of tumor cells. Methods MTT assay, apoptosis assay and morphologic observation were applied to evaluate the growth of human colorectal cancer SW116 cells, LoVo cells and human gastric cancer MKN-28 cells at different pHe values. The expression of Bcl-2 and survivin genes were tested by real-time PCR. Results Compared with pHe7.4, the viabilities of all three cell lines were enhanced at pHe 6.8 (P<0.05). Morphological observation and apoptosis assay confirmed that the viabilities of tumor cells at pHe6.8 were as same as those at pHe 7.4. At pHe 6.8, the expression of Bcl-2 was decreased significantly (P<0.05) while the expression of survivin didn't show a significant change. Conclusion The low extracellular pH value induces the growth of tumor cells without viability or morphology change. Meanwhile, the expression of apoptosisrelated gene, Bcl-2 is affected.
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Key words:
- Tumor drug resistance /
- pH value /
- Microenvironment /
- Apoptosis
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