端粒酶逆转录酶（hTERT）脱氧核酶对A549/DDP细胞生长影响的实验研究
[An experimental study of telomerase reverse transcriptase (hTERT) DNAzyme on growth of A549/DDP cells].
作者信息
Yu Bingxiang, Zhu Jie, Liu Youning, Zheng Xiaofei
机构信息
Department of Respiratory Medicine, Chinese PLA General Hospital, Beijing 100853, P.R.China.
出版信息
Zhongguo Fei Ai Za Zhi. 2006 Oct 20;9(5):405-8. doi: 10.3779/j.issn.1009-3419.2006.05.02.
BACKGROUND
Telomerase expresses in many cancers and may contribute to drug-resistance. The aim of this study is to observe the effect of telomerase reverse transcriptase (hTERT) DNAzyme on growth of A549/DDP cells and to explore the possibility of telomerase as a new target in treatment of drug resistance for lung cancer.
METHODS
An hTERT DNAzyme was composed. Telomerase activity was measured by telomeric repeat amplification protocol (TRAP) modified from Kim's method. MTT was used to show the influence of hTERT DNAzyme and cisplatin on A549/DDP cells.
RESULTS
The telomerase activity of A549/DDP cells was down-regulated by hTERT DNAzyme in a dose-dependent manner. The growth inhibition rate of A549/DDP cells was 32.9% by hTERT DNAzyme of 0.25μmol/L, and 60.5% by hTERT DNAzyme combined with 3mg/L cisplatin. The CDI of hTERT DNAzyme and cisplatin was 0.9.
CONCLUSIONS
hTERT DNAzyme can inhibit the growth of A549/DDP cells and has a synergistic effect with cisplatin. It is suggested that telomerase may be a new target in treatment of drug-resistant lung cancer cells.
背景
端粒酶在多种癌症中表达，可能与耐药性有关。本研究旨在观察端粒酶逆转录酶（hTERT）脱氧核酶对A549/DDP细胞生长的影响，并探讨端粒酶作为肺癌耐药治疗新靶点的可能性。
方法
构建hTERT脱氧核酶。采用改良的Kim法通过端粒重复序列扩增法（TRAP）检测端粒酶活性。用MTT法检测hTERT脱氧核酶和顺铂对A549/DDP细胞的影响。
结果
hTERT脱氧核酶可使A549/DDP细胞的端粒酶活性呈剂量依赖性下调。0.25μmol/L的hTERT脱氧核酶使A549/DDP细胞的生长抑制率为32.9%，hTERT脱氧核酶联合3mg/L顺铂时生长抑制率为60.5%。hTERT脱氧核酶与顺铂的协同指数为0.9。
结论
hTERT脱氧核酶可抑制A549/DDP细胞生长，并与顺铂具有协同作用。提示端粒酶可能是耐药肺癌细胞治疗的新靶点。
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