【摘要】 目的:初步探讨低氘水(deuterium-depleted water,DDW)在体内外对人肺癌细胞增殖的抑制作用及其可能机制。方法:MTT法检测DDW对肺癌A549细胞和正常人胚肺成纤维细胞HLF-1增殖的抑制作用,TUNEL法检测A549细胞凋亡情况,流式细胞仪检测细胞周期的变化。建立BALB/c裸鼠人肺癌H460细胞移植瘤模型,低氘水饮用60d后观察裸鼠移植瘤的生长情况。结果:与对照组比较,培养10h时体积分数为0.0025%、0.0050%和0.0105%的DDW对A549细胞增殖具有显著抑制作用(P<0.05),随后抑制作用消失,48h后又逐渐出现抑制现象,72h抑制作用显著(P<0.05);相同条件下不同体积分数的DDW对正常人胚肺成纤维细胞HLF-1无显著抑制作用。TUNEL染色显示,0.005%DDW作用后A549细胞出现凋亡,凋亡率显著高于对照组细胞[(25.38±3.90)%vs(10.87±1.11)%),P<0.05]。流式细胞仪检测显示,DDW作用后A549细胞S期细胞显著增加(P<0.05)。人肺癌细胞H460移植瘤裸鼠饮用DDW后,能够明显提高裸鼠的生活质量,抑瘤率达30.08%。结论:DDW对肺癌细胞增殖的抑制作用仅限于一定的剂量范围,且具有波动性和时段性的特点;其机制可能与诱导肺癌细胞S期阻滞和细胞凋亡有关。更多还原

【Abstract】 Objective:To explore the in vitro and in vivo inhibitory effects of deuterium-depleted water(DDW) on the proliferation of human lung carcinoma cells,and to explore the possible mechanism.Methods:The inhibitory effect of DDW on the proliferation of human lung carcinoma A549 cells and human embryonic lung fibroblast HLF-1 cells was examined by MTT assay;apoptosis of A549 cells was examined by TUNEL;and cell cycle was analyzed by flow cytometry.Mouse model of lung carcinoma was established by inoculating human lung carcinoma H460 cells into BALB/c nude mice,and the growth of implanted tumors was observed after DDW treatment for 60 d.Results:Compared with control group,A549 cells treated with 0.0025%,0.0050% or 0.0105% DDW showed significantly decreased proliferation 10 h after treatment(P<0.01).Then the inhibitory effects of DDW gradually disappeared,but appeared 48 h later again,with the inhibitory effects at 72 h being significant(P<0.05).DDW at the same dosages showed no inhibition on the proliferation of HLF-1 cells(P>0.05).TUNEL assay verified the apoptosis of DDW-treated A549 cells,and the apoptosis rate of DDW-treated A549 cells was significantly higher than that of control group([45.30±4.21]% vs [22.25±0.30]%,P<0.01).Cells in S phase were significantly increased in DDW-treated A549 cells compared with those in the control group(P<0.05).The life quality of H460 cell-inoculated nude mice treated with DDW was greatly improved,with the tumor inhibition rate being 30.08%.Conclusion:DDW can inhibit the proliferation of lung cancer cells within a certain range of dosage and in a fluctuating pattern;its mechanism might be associated with induction of apoptosis and cell cycle arrest in S phase of tumor cells.更多还原