Factors affecting sensitivity to EO9 in rodent and human tumour cells in vitro: DT-diaphorase activity and hypoxia.
Factors affecting sensitivity to EO9 in rodent and human tumour cells in vitro: DT-diaphorase activity and hypoxia.
复制标题
影响啮齿动物和人类肿瘤细胞体外对 EO9 敏感性的因素：DT-心肌黄酶活性和缺氧。
DOI：
10.1016/0959-8049(94)90134-1
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Stratford,IJ
中科院分区：
文献类型：
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作者：
Robertson,N;Haigh,A;Adams,GE;Stratford,IJ
评价了23种人类肿瘤细胞系（肺、乳腺和结肠）和8种啮齿动物细胞系对醌类抗癌药物EO 9 [3-羟甲基-5-氮丙啶基-1-甲基-2-（1H吲哚-4，7-二酮）丙-β-烯-α-o 1]的敏感性。敏感性进行了比较与细胞内水平的DT-心肌黄酶，和细胞系显示最高的酶活性往往是最敏感的EO 9。DT-黄递酶在确定药物敏感性中的作用通过使用酶抑制剂双香豆素来证实，双香豆素保护含有高水平DT-黄递酶的细胞免受EO 9的细胞毒性作用。缺氧增加细胞的细胞毒性含有低，但不高水平的DT-心肌黄酶，这意味着1-和2-电子还原活化过程可以是重要的表达EO 9毒性。它的结论是，EO 9是一个潜在的有用的代理在酶导向的方法中使用的生物还原药物在癌症治疗。
Twenty-three human tumour cell lines (lung, breast, and colon) and eight rodent cell lines were evaluated for their sensitivity to the quinone-based anticancer drug EO9 [3-hydroxymethyl-5-aziridinyl-1-methyl-2-(1H indole-4,7-dione)prop-β-en-α-o1]. Sensitivity was compared with the intracellular levels of DT-diaphorase, and cell lines showing highest enzyme activity tended to be the most sensitive to EO9. The role of DT-diaphorase in determining drug sensitivity was confirmed by using the enzyme inhibitor dicoumarol, which protects cells containing high levels of DT-diaphorase from the cytotoxic action of EO9. Hypoxia increased the cytotoxicity of cells containing low but not high levels of DT-diaphorase, implying that both 1- and 2-electron reductive activation processes can be important for expression of EO9 toxicity. It is concluded that EO9 is a potentially useful agent in the enzyme directed approach to the use of bioreductive drugs in cancer therapy.