诱导型一氧化氮合酶影响吲哚醌类化合物抗肿瘤活性的实验研究  

The Study on the Effect of Inducible Nitric Oxide Synthase on Tumour Cells Sensitivity to Indoquinine-based Compounds

作　　者：孔肇路[1] 金一尊[1] 

机构地区：[1]复旦大学放射医学研究所,上海200032

出　　处：《标记免疫分析与临床》2008年第3期162-166,共5页Labeled Immunoassays and Clinical Medicine

基　　金：国家自然科学基金项目(No30500143);复旦新进校青年教师事业发展起步计划

摘　　要：观察诱导型一氧化氮合酶（iducible nitric oxide synthase,iNOS）对新型吲哚醌类生物还原化合物630和630Ac的抗肿瘤活性和乏氧选择性的影响。以人纤维肉瘤细胞HT1080及其iNOS基因转染的细胞克隆为研究对象,噻唑蓝法检测不同iNOS活性的细胞克隆对化合物630和630Ac化学敏感性的差异;比较乏氧和有氧条件下半数抑制浓度（IC50）的差异;流式细胞术观察化合物对细胞周期的影响。630Ac和630在实验中均显示出较强的抗肿瘤活性,且630Ac的细胞毒性强于630;而iNOS转染的细胞对630和630Ac敏感性较亲本细胞HT1080有所下降,IC50分别高1～7倍左右。氧对630的细胞毒性无显著影响,而630Ac则具有较好的乏氧选择性细胞毒作用,尤其是对iNOS转基因细胞,有氧和乏氧条件下IC50相差4～7倍。提示iNOS活性的增强会引起肿瘤细胞对化合物630和630Ac敏感性的降低。To observe the effect of iNOS on tumour cells chemosensitivity to indoquinine-based bioreductive compounds 630 and 630Ac, human filbrosarcoma cell line, HT1080 and its iNOS gene transfected clones, were exposed to 630 and 630Ac in air and under hypoxia, respectively. IC50 was calculated by MTT assay to measure cellular sensitivity to above compunds, and the change of cell cycle after exposed in 630 or 630Ac were plot by flow cytometric analysis. It is found that both 630 and 630Ac were cytotoxicity compounds, and 630Ac was more toxic than 630. Cells with higher iNOS activity exhibited resistance to above compounds, whose IC50 were increased 1-7 folds comparing to its parent cells. Meanwhile, 630Ac could cause more cell damage under hypoxia, especially in those iNOS-gene transfected cells. It is suggested that iNOS could be a candidate drug-resistant gene.

关 键 词：生物还原 诱导型一氧化氮合酶 化学敏感性 乏氧 

分 类 号：R730.5[医药卫生—肿瘤]