The cytocidal action of metronidazole in combination with other antineoplastic agents.
The cytocidal action of metronidazole in combination with other antineoplastic agents.
复制标题
甲硝唑与其他抗肿瘤药联合使用的杀细胞作用。
DOI：
10.1016/s0305-7372(79)80013-4
复制
发表时间：
1979
影响因子：
11.8
通讯作者：
G. Giles
中科院分区：
文献类型：
--
作者：
J. Kelly;T. W. Hannam;G. Giles
甲硝唑（Flagyl）已被证明是几种小鼠肿瘤系统中的有效放射增敏剂（1，9，10，12）。还清楚的是，针对细菌显示的杀细胞作用也可以针对哺乳动物细胞有效。Sutherland（14）在研究中研究了该药物的化疗作用，结果表明该药物优先杀死多细胞球体中的非循环细胞。甲硝唑的杀细胞作用取决于细胞类型、药物浓度、温度、孵育持续时间和氧浓度。在实体瘤中，很可能存在大量的缺氧细胞，这些细胞是非循环的，并且可能对标准细胞毒性剂具有抗性。因此，甲硝唑与其它抗肿瘤药物的组合在杀死逃避单独的周期特异性α 1-期特异性药物的作用的细胞方面可能具有显著的价值，这是需要进一步研究的领域。在这项研究中，我们评估了甲硝唑在体外单层培养，建立从化学诱导的小鼠结肠肿瘤的行动。还测量了单独的和与甲硝唑组合的标准抗肿瘤剂的杀细胞作用。在体内实验中，对甲硝唑与5-氟尿嘧啶（5-FU）和甲氨蝶呤（MTX）联合应用时的转化延迟进行了研究。
Metronidazole (Flagyl) has been shown to be an effective radiosensitizer in several murine tumour systems (1, 9, 10, 12). It is also clear that the cytocidal action shown against bacteria may also be effective against mammalian cell~. The chemotherapeutic effect of the drug was investigated by Sutherland (14) in studies which demonstrated that the drug preferentially killed non-cycling ceils in multicellular spheroids. The cytocidal effect of metronidazole is dependent upon cell type, drug concentration, temperature, duration of incubation and oxygen concentration. Within solid tumours it is likely that there are significant numbers of hypoxic cells which are non-cycling and probably resistant to standard cytotoxic agents. Thus the combination of metronidazole with other antineoplastic agents could be of significant value in killing cells which escape the action of cycle specific o1" phase specific agents alone and it is an area requiring further investigation. In this study we have assessed the action of metronidazole on in vitro monolayer cultures, established from a chemically induced murine colonic tumour. The cytocidal action of standard antineoplastic agents alone and in combination with metronldazole is also measured. Studies of turnout delay during in vivo experiments have been made combining metronidazole with 5-fluorouracil (5-FU) and methotrexate (MTX).