Teicher B A, Gunner L J, Roach J A
Br J Cancer. 1985 Dec;52(6):833-9. doi: 10.1038/bjc.1985.266.
The potential of cis-diamminedichloroplatinum(II) (CDDP), trans-di(2-nitroimidazole)dichloro-platinum(II) (NIPt), trans-di(2-amino-5-nitrothiazole)dichloroplatinum(II) (Plant), cis-(1,2-diamino-4-nitrobenzene)dichloroplatinum(II) (Plato), and cis-di-pyridinedichloroplatinum(II) (PyPt) to act as chemosensitizers of mitomycin C cytotoxicity toward EMT6 cells under oxygenated and hypoxic conditions has been assessed. Cells were given a 1 h treatment with the platinum complex under oxygenated or hypoxic conditions and then an additional one hour of exposure to the combination. Two concentrations of each platinum complex, 0.1 and 0.01 microM, were tested in combination with mitomycin C at 1, 0.1 and 0.01 microM. The results were analyzed via isobolograms. Under oxygenated conditions the combinations of the various platinum complexes and mitomycin C produced approximately a 2-3-fold enhancement in cell killing. Under hypoxic conditions enhancements of 5-fold, 20-fold and 60-fold were obtained with CDDP and 1, 0.1 and 0.01 microM mitomycin C, respectively. The combinations of 0.1 microM NIPT and mitomycin C under hypoxic conditions were 30-60-fold more cytotoxic than expected by additivity. With 0.01 microM NIPT a 15-23-fold enhancement of mitomycin C cytotoxicity was observed. The Plant-mitomycin C combinations produced a 5-14-fold enhancement in cell killing under hypoxic conditions. Under hypoxic conditions the combinations of 0.1 microM Plato and mitomycin C were 30-60-fold more cytotoxic than expected. At 0.01 microM Plato an 8-16-fold enhancement in cytotoxicity was observed under hypoxic conditions. PyPt and mitomycin C produced an 8-16-fold enhancement in cytotoxicity under hypoxic conditions. Overall, the platinum complexes containing radiosensitizing nitroaromatic groups were no more active in producing enhanced effects than cis-diamminedichloroplatinum(II).
已评估顺二氯二氨铂（II）（CDDP）、反二（2-硝基咪唑）二氯铂（II）（NIPt）、反二（2-氨基-5-硝基噻唑）二氯铂（II）（Plant）、顺-（1,2-二氨基-4-硝基苯）二氯铂（II）（Plato）和顺二吡啶二氯铂（II）（PyPt）在有氧和缺氧条件下作为丝裂霉素C对EMT6细胞细胞毒性的化学增敏剂的潜力。细胞在有氧或缺氧条件下用铂配合物处理1小时，然后再额外暴露于联合用药1小时。测试了每种铂配合物的两种浓度，即0.1和0.01微摩尔，与1、0.1和0.01微摩尔的丝裂霉素C联合使用。通过等效线图分析结果。在有氧条件下，各种铂配合物与丝裂霉素C的联合用药在细胞杀伤方面产生了约2至3倍的增强。在缺氧条件下，CDDP与1、0.1和0.01微摩尔丝裂霉素C联合使用时，细胞杀伤增强倍数分别为5倍、20倍和60倍。在缺氧条件下，0.1微摩尔NIPT与丝裂霉素C的联合用药的细胞毒性比预期的相加效应高30至60倍。使用0.01微摩尔NIPT时，观察到丝裂霉素C细胞毒性增强了15至23倍。Plant与丝裂霉素C的联合用药在缺氧条件下使细胞杀伤增强了5至14倍。在缺氧条件下，0.1微摩尔Plato与丝裂霉素C的联合用药的细胞毒性比预期高30至60倍。在0.01微摩尔Plato时，在缺氧条件下观察到细胞毒性增强了8至16倍。PyPt与丝裂霉素C在缺氧条件下使细胞毒性增强了8至16倍。总体而言，含有放射增敏硝基芳基基团的铂配合物在产生增强效应方面并不比顺二氯二氨铂（II）更具活性。
