首页|期刊导航|中华医学杂志（英文版）|Highly expressed N1-acetylpolyamine oxidase detoxifies polyamine analogue N1-cyclopropylmethyl-N11-ethylnorspermine in human lung cancer cell line A549
中华医学杂志（英文版）2009，Vol.122Issue(12)：1394-1399,6.DOI:10.3760/cma.j.issn.0366-6999.2009.12.007
Highly expressed N1-acetylpolyamine oxidase detoxifies polyamine analogue N1-cyclopropylmethyl-N11-ethylnorspermine in human lung cancer cell line A549
Highly expressed N1-acetylpolyamine oxidase detoxifies polyamine analogue N1-cyclopropylmethyl-N11-ethylnorspermine in human lung cancer cell line A549
摘要
Abstract
Background The critical roles of polyamines in cell growth and differentiation have made polyamine metabolic pathway a promising target for antitumor therapy. Recent studies have demonstrated in vitro that some antitumor polyamine analogues could be used as substrates and oxidized by purified recombinant human N1-acetylpolyamine oxidase (APAO, an enzyme that catabolizes natural polyamines), indicating a potential role of APAO in determining the sensitivity of cancer cells to specific antitumor analogues. This study evaluated, in vivo, the effect of APAO on cytotoxicity of antitumor polyamine analogue, N1-cyclopropylmethyI-N11-ethylnorspermine (CPENS) and its mechanism when highly expressed in human lung cancer line A549.Methods A clone with high expression of APAO was obtained by transfecting A549 lung cancer cell line with pcDNA3.1/APAO plasmid and selecting with quantitative realtime PCR and APAO activity assay. Cell proliferation was determined by MTT method and apoptosis related events were evaluated by DNA fragmentation, sub-G1/flow cytometric assay, western blotting (for cytochrome C and Bax) and colorimetric assay (for casapse-3 activity). Results A clone highly expressing APAO was obtained. High expression of APAO in A549 cells inhibited accumulation of CPENS, decreased their sensitivity to the toxicity of CPENS and prevented CPENS induced apoptosis. Conclusion These results indicate a new drug resisting, mechanism in the tumor cells. High expression of APAO can greatly decrease the sensitivity of tumor cells to the specific polyamine analogues by detoxitying those analogues and prevent analogue induced apoptosis.关键词
N1-acetylpolyamine oxidase/lung cancer cell/polyamine analogue/drug resistanceKey words
N1-acetylpolyamine oxidase/lung cancer cell/polyamine analogue/drug resistance分类
医药卫生引用本文复制引用
HAN Yu,REN Yu-san,CAO Chun-yu,REN Dong-ming,ZHOU Yong-qin,WANG Yan-lin..Highly expressed N1-acetylpolyamine oxidase detoxifies polyamine analogue N1-cyclopropylmethyl-N11-ethylnorspermine in human lung cancer cell line A549[J].中华医学杂志（英文版）,2009,122(12):1394-1399,6.基金项目
This work was supported by grants from the National Natural Science Foundation of China (No. 30772590) and Natural Science Foundation of Hubei Department of Education (No. D200713003). （No. 30772590）
