Effect of aspirin on induction of apoptosis in HT-29 human colon adenocarcinoma cells
Effect of aspirin on induction of apoptosis in HT-29 human colon adenocarcinoma cells
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DOI：
10.1016/s0006-2952(97)00400-0
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发表时间：
1998-01-01
影响因子：
5.8
通讯作者：
Rigas, B
中科院分区：
文献类型：
--
作者：
Qiao, L;Hanif, R;Rigas, B
阿司匹林（ASA）和其他非甾体抗炎药（NSAIDs）抑制结直肠肿瘤的发生。细胞凋亡是组织质量稳态的关键决定因素，并可能在癌变中发挥作用。我们使用比以前更灵敏的方法研究了ASA对人结肠癌细胞系存活的影响。ASA在浓度大于或等于mM时诱导HT-29结肠腺癌细胞凋亡，结果如下：(a)荧光显微镜和半薄细胞切片检查细胞的形态学变化与细胞凋亡一致，(b) DNA链断裂：tdt介导的dUTP nick end labeling （TUNEL）在3mm处72小时呈阳性，45%的细胞呈tdt介导的dUTP nick end labeling （TUNEL）阳性，70%的细胞呈彗星试验阳性。电镜也证实了ASA对细胞凋亡的诱导作用。asa诱导的细胞凋亡与：(a)基因组DNA电泳上的阶梯图或(b)流式细胞术上的亚二倍体峰无关。在标准形态学评估中几乎没有凋亡小体，仅在半薄切片上检测到少量凋亡小体。由于上述原因，ASA诱导的细胞凋亡是“非典型的”，ASA诱导的细胞凋亡的不寻常特征，除了它们的分类学价值外，可能为控制细胞凋亡过程的机制或该化合物的癌症化学预防特性提供线索。这些发现表明ASA诱导人结肠癌细胞凋亡，支持了细胞凋亡可能是非甾体抗炎药抑制结肠癌发生机制的假设。这些发现应该在动物和/或体内临床研究中进行检验。(C) 1998爱思唯尔科学有限公司
Aspirin (ASA) and other nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit colorectal tumorigenesis. Apoptosis is a critical determinant of tissue mass homeostasis and may Flay a role in carcinogenesis. We studied the effect of ASA on the survival of a human colon cancer cell line using more sensitive methods than we had applied previously. ASA induced apoptosis in HT-29 colon adenocarcinoma cells at concentrations greater than or equal to mM as established by: (a) morphological changes consistent with apoptosis in cells examined by fluorescence microscopy and semi-thin cell sections, and (b) DNA strand breaks: 45% of the cells were TdT-mediated dUTP nick end labeling (TUNEL) positive at 3 mM at 72 hr, and 70% were positive by the comet assay. Electron microscopy also confirmed the induction of apoptosis by ASA. ASA-induced apoptosis was not associated with: (a) a ladder pattern on genomic DNA electrophoresis, or (b) a subdiploid peak on flow cytometry. Apoptotic bodies were virtually absent on standard morphological assessments and only a few were detected on semi-thin sections. For the above reasons, this apoptosis induced by ASA is ''atypical,'' and the unusual features of ASA-induced apoptosis, besides their taxonomic value, may offer clues to the mechanisms that control the process of apoptosis or perhaps the cancer chemopreventive properties of this compound. These findings demonstrate that ASA induces apoptosis in human colon cancer cells, bolstering the hypothesis that apoptosis may be a mechanism by which NSAIDs inhibit colon carcinogenesis. These findings should be examined in animal and/or clinical research studies in vivo. (C) 1998 Elsevier Science Inc.