Cervantes A, Pinedo H M, Lankelma J, Schuurhuis G J
Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
Cancer Lett. 1988 Aug 15;41(2):169-77. doi: 10.1016/0304-3835(88)90113-9.
The role of oxygen-derived free radicals in the cytotoxicity of doxorubicin (Dox) was studied in a Dox sensitive human ovarian cancer cell line (A2780) and its multidrug resistant counterpart (2780AD) using reactive oxygen scavengers. In both cell lines, a significant inhibition of Dox toxicity was found after treatment with the hydroxyl radical scavengers, N-acetylcysteine, sodium benzoate and dimethyl sulfoxide, but not with mannitol. The protection was similar in sensitive and resistant cells: 13-39% less growth inhibition was found at Dox concentrations of 0.2 and 0.5 microM for A2780 as well as at 20 and 50 microM for 2780AD. This protection was not due to effects of the scavengers on Dox accumulation, as shown by uptake experiments with radio-labelled Dox. The superoxide anion free radical scavenger ascorbic acid or the enzyme superoxide dismutase as well as the hydrogen peroxide scavenger catalase did not protect cells against Dox-induced cell growth inhibition. Preloading the cells with the enzymes, a treatment which resulted in a two to nine-fold increase in their cellular contents, was not effective either. It is concluded that hydroxyl radicals, but not superoxide anion or hydrogen peroxide likely play a role in the antitumor activity of Dox in sensitive and resistant human ovarian cancer cells.
使用活性氧清除剂，在对阿霉素（Dox）敏感的人卵巢癌细胞系（A2780）及其多药耐药对应细胞系（2780AD）中研究了氧衍生自由基在阿霉素细胞毒性中的作用。在这两种细胞系中，用羟基自由基清除剂N-乙酰半胱氨酸、苯甲酸钠和二甲基亚砜处理后，发现阿霉素毒性受到显著抑制，但用甘露醇处理则未出现这种情况。敏感细胞和耐药细胞中的保护作用相似：在阿霉素浓度为0.2和0.5微摩尔时，A2780细胞的生长抑制减少13 - 39%，在阿霉素浓度为20和50微摩尔时，2780AD细胞的生长抑制也减少13 - 39%。如用放射性标记的阿霉素摄取实验所示，这种保护作用并非由于清除剂对阿霉素积累的影响。超氧阴离子自由基清除剂抗坏血酸或酶超氧化物歧化酶以及过氧化氢清除剂过氧化氢酶均不能保护细胞免受阿霉素诱导的细胞生长抑制。用这些酶对细胞进行预加载处理（该处理使细胞内含量增加了2至9倍）也无效。结论是，羟基自由基而非超氧阴离子或过氧化氢可能在阿霉素对敏感和耐药人卵巢癌细胞的抗肿瘤活性中起作用。
