McMillan T J, Stephens T C, Steel G G
Br J Cancer. 1985 Dec;52(6):823-32. doi: 10.1038/bjc.1985.265.
The development of resistance to melphalan, cis-platinum and cyclophosphamide has been examined in the MT murine mammary carcinoma. A gradual decrease in therapeutic response was detected using growth delay and clonogenic cell survival during repeated drug treatment. A slow rate of resistance development, a gradual change in the slope of the dose-survival curves and the inability of 180 mg kg-1 cyclophosphamide to bring about a reduction in tumour response at a faster rate than 60 mg kg-1 cyclophosphamide suggest that resistance development was not due to the selection of a pre-existing highly drug resistant sub-population of tumour cells. Partial drug-resistance is proposed as one possible reason for the apparent inconsistency between these data and existing models of drug-resistance development. The drug-resistant lines were characterized for karyotype, DNA content and cell volume, but only the cyclophosphamide-resistant line showed any significant difference from the wild-type tumour. Cross-resistance studies revealed some inconsistencies with previous reports. Also, resistance to cyclophosphamide developed more quickly in the line which was resistant to melphalan, than in the wild-type tumour, despite the initial appearance of little cross-resistance. This increased rate of resistance development may be important in salvage chemotherapy.
在MT小鼠乳腺癌中研究了对美法仑、顺铂和环磷酰胺的耐药性发展情况。在重复药物治疗期间，通过生长延迟和克隆形成细胞存活情况检测到治疗反应逐渐降低。耐药性发展速度缓慢，剂量-存活曲线斜率逐渐变化，且180mg/kg环磷酰胺未能比60mg/kg环磷酰胺更快地降低肿瘤反应，这表明耐药性发展并非由于预先存在的高度耐药肿瘤细胞亚群的选择。部分耐药性被认为是这些数据与现有耐药性发展模型之间明显不一致的一个可能原因。对耐药细胞系进行了核型、DNA含量和细胞体积的表征，但只有环磷酰胺耐药细胞系与野生型肿瘤表现出任何显著差异。交叉耐药性研究揭示了与先前报道的一些不一致之处。此外，对美法仑耐药的细胞系中，对环磷酰胺的耐药性发展比野生型肿瘤更快，尽管最初几乎没有交叉耐药性。这种增加的耐药性发展速度在挽救化疗中可能很重要。
