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低氘水通过凋亡抑制人肺癌细胞生长。

Deuterium-depleted water inhibits human lung carcinoma cell growth by apoptosis.

作者信息

Cong Feng-Song, Zhang Ya-Ru, Sheng Hong-Cai, Ao Zong-Hua, Zhang Su-Yi, Wang Ju-Yong

机构信息

College of Life Sciences and Technology, Shanghai Jiaotong University, Shanghai 200240;

出版信息

Exp Ther Med. 2010 Mar;1(2):277-283. doi: 10.3892/etm_00000043. Epub 2010 Mar 1.

Abstract

To investigate the in vivo and in vitro inhibitory effects of deuterium-depleted water (DDW) on human lung cancer and the possible mechanisms underlying these effects, we cultured and treated human lung carcinoma cell line A549 and human embryonic lung fibroblasts HLF-1 with various concentrations of DDW from 2 to 72 h. Cellular growth inhibition rates were determined using the 3-(4, 5-dimethyldiazol-2-yl)-2, 5-diphenyltetrazolium-bromide) (MTT) proliferation assay. A549 cells were treated with 50±5 ppm DDW, and the morphology and structure of cells were observed by scanning electron microscopy (SEM). We observed alterations in the cellular skeleton by transmission electron microscopy (TEM) and changes in cell cycle by flow cytometry. Our data showed that DDW significantly inhibited the proliferation of A549 cells at a specific time point, and cells demonstrated the characteristic morphological changes of apoptosis under SEM and TEM. The length of the S phase increased significantly in cells treated with 50 ppm DDW, whereas the G0 to G1 phase and G2 to M phase were decreased. We observed DDW-induced cellular apoptosis using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and DNA fragment analyses. In addition, we established a tumor transplantion model by injecting H460 tumor cells into subcutaneous tissue of BALB/c mice treated with DDW for 60 days. We determined the tumor inhibition rate of treated and control groups and found that the tumor weight was significantly decreased and the tumor inhibition rate was approximately 30% in the DDW group. We conclude that DDW is a promising new anticancer agent with potential for future clinical application.

摘要

为了研究去氘水(DDW)对人肺癌的体内和体外抑制作用以及这些作用的潜在机制,我们用2至72小时不同浓度的DDW培养并处理人肺癌细胞系A549和人胚肺成纤维细胞HLF-1。使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)增殖试验测定细胞生长抑制率。用50±5 ppm的DDW处理A549细胞,通过扫描电子显微镜(SEM)观察细胞的形态和结构。通过透射电子显微镜(TEM)观察细胞骨架的变化,通过流式细胞术观察细胞周期的变化。我们的数据表明,DDW在特定时间点显著抑制A549细胞的增殖,并且在SEM和TEM下细胞表现出凋亡的特征性形态变化。用50 ppm DDW处理的细胞中S期长度显著增加,而G0至G1期和G2至M期减少。我们使用末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)和DNA片段分析观察到DDW诱导的细胞凋亡。此外,我们通过将H460肿瘤细胞注射到用DDW处理60天的BALB/c小鼠的皮下组织中建立了肿瘤移植模型。我们测定了治疗组和对照组的肿瘤抑制率,发现DDW组的肿瘤重量显著降低,肿瘤抑制率约为30%。我们得出结论,DDW是一种有前景的新型抗癌剂,具有未来临床应用的潜力。

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