8-氯腺苷诱导多种肿瘤细胞凋亡

目的研究８－氯腺苷（８ＣＡ）对肿瘤细胞生长和凋亡的作用。方法以不同浓度的８ＣＡ处理在体外培养的肿瘤细胞株,使用ＭＴＴ法测定细胞生长曲线,以光学显微镜、流式细胞仪和ＤＮＡ片段化分析细胞凋亡。结果１０μｍｏｌ／Ｌ８ＣＡ处理４８小时,可显著抑制肿瘤细胞的增殖。ＭＴＴ曲线测定发现,所试细胞对８ＣＡ的敏感程度依次为：ＨＬ－６０白血病细胞系最敏感,ＭＧｃ－８０３胃癌细胞系次之,ＮＩＨ３Ｔ３正常纤维母细胞最不敏感。进一步研究发现,８ＣＡ抑制ＨＬ－６０和ＭＧｃ－８０３肿瘤细胞生长的机制是诱导肿瘤细胞凋亡（ａｐｏｐｔｏｓｉｓ）,肿瘤细胞具有典型的细胞凋亡形态特征,基因组ＤＮＡ发生断裂,并在琼脂糖凝胶中呈现梯形图谱,流式细胞仪分析可检出凋亡峰。结论８ＣＡ可作为细胞凋亡诱导剂用于肿瘤治疗。

8-chloro-adenosine induced apoptosis in various human tumor cell lines

OBJECTIVE: To study the effect of 8-Chloro-adenosine (8CA) on tumor cell growth and apoptosis. METHODS: Tumor and normal cell lines were treated with 8CA at different concentrations and cell growth was analysed by MTT assay. Cell apoptosis was evaluated by light microscopy, flow cytometry and chromosome DNA fragmentation. RESULTS: Treatment with 8CA at 10 mumol/L remarkably inhibited tumor cell growth. HL-60 promyelocytic leukemia cell line was more sensitive to 8CA than MGc-803 gastric mucoid adenocarcinoma cell line. NIH3T3 cells were relatively resistant to 8CA. The IC50 of HL-60 and MGc-803 cells was 1.2 mumol/L and 1.8 mumol/L, respectively, while that of NIH3T3 cells was 12 mumol/L. Further study showed that 8CA induced HL-60 and MGc-803 cell death characterized by apoptotic phenotypes, DNA content changes and chromosome DNA fragmentation. CONCLUSION: 8CA is a potential agent for tumor chemotherapy.