Twentyman P R, Wright K A
MRC Clinical Oncology, Cambridge, UK.
Cancer Chemother Pharmacol. 1991;29(1):24-8. doi: 10.1007/BF00686331.
We investigated the chemosensitisation of the parental EMT6 mouse mammary tumour cell line by low doses of cyclosporin A (CsA). This cell line has not previously been exposed to cytotoxic drugs but expresses low levels of P-glycoprotein. We produced greater than 2-fold sensitisation to doxorubicin, colchicine and vincristine using 0.084 microM (0.1 micrograms/ml) CsA. Cellular accumulation of doxorubicin and daunorubicin was also increased by this dose. In the MDR subline EMT6/AR1.0, much higher doses of CsA were required to effect optimal restoration of doxorubicin or daunorubicin accumulation. The effects of CsA on the parent line could not be increased by extended preincubation of cells with the sensitiser. These effects of CsA in the EMT6 parent cell line occur at a dose that is 1 order of magnitude lower than those previously reported to produce significant chemosensitisation.
我们研究了低剂量环孢菌素A（CsA）对亲代EMT6小鼠乳腺肿瘤细胞系的化学增敏作用。该细胞系此前未接触过细胞毒性药物，但P-糖蛋白表达水平较低。使用0.084微摩尔/升（0.1微克/毫升）的CsA，我们对阿霉素、秋水仙碱和长春新碱产生了超过2倍的增敏作用。该剂量还增加了阿霉素和柔红霉素的细胞内蓄积。在多药耐药亚系EMT6/AR1.0中，需要更高剂量的CsA才能实现阿霉素或柔红霉素蓄积的最佳恢复。用增敏剂对细胞进行延长预孵育并不能增强CsA对亲代细胞系的作用。CsA在EMT6亲代细胞系中的这些作用发生的剂量比先前报道产生显著化学增敏作用的剂量低1个数量级。
