Twentyman P R, Wright K A, Fox N E
MRC Clinical Oncology and Radiotherapeutics Unit, Cambridge, UK.
Br J Cancer. 1990 Feb;61(2):279-84. doi: 10.1038/bjc.1990.52.
We have established a subline (EMT6/VRP) of the mouse tumour cell line EMT6/P with acquired resistance to the calcium transport blocker verapamil (VRP). The subline was 4-fold resistant to the cytoxicity of VRP alone compared with the parent line but of similar sensitivity to adriamycin, vincristine or colchicine. EMT6/VRP cells growing in 75 micrograms ml-1 VRP were morphologically different from and larger in diameter than EMT6/P cells, but these two parameters reverted almost to normal within 3 days of VRP removal, although resistance was retained. Expression of an mRNA coding for P-glycoprotein was similar in EMT6/VRP and the parent cell line, although considerable hyperexpression was seen in a multidrug resistant subline, EMT6/AR1.0. Cellular accumulation of both 3H-daunorubicin and 3H-VRP were greater in EMT6/VRP than in the parent line. Sensitisation to adriamycin by 3.3 micrograms ml-1 VRP was, however, somewhat reduced in EMT6/VRP (i.e. to 6.1-fold) compared with the 11-fold sensitisation seen in the parent line. It is clear that resistance to VRP seen in this cell line occurs via a different mechanism from the resistance to drugs such as adriamycin, vincristine and colchicine seen in multidrug resistant cell lines.
我们已经建立了小鼠肿瘤细胞系EMT6/P的一个亚系（EMT6/VRP），该亚系对钙转运阻滞剂维拉帕米（VRP）具有获得性抗性。与亲代细胞系相比，该亚系对单独使用VRP的细胞毒性具有4倍抗性，但对阿霉素、长春新碱或秋水仙碱的敏感性相似。在含有75微克/毫升VRP的培养基中生长的EMT6/VRP细胞在形态上与EMT6/P细胞不同，直径也更大，但在去除VRP后3天内，这两个参数几乎恢复正常，尽管抗性仍然保留。编码P-糖蛋白的mRNA在EMT6/VRP和亲代细胞系中的表达相似，尽管在多药耐药亚系EMT6/AR1.0中观察到相当程度的过表达。3H-柔红霉素和3H-VRP在EMT6/VRP中的细胞积累均高于亲代细胞系。然而，与亲代细胞系中观察到的11倍增敏相比，3.3微克/毫升VRP对EMT6/VRP中阿霉素的增敏作用有所降低（即降至6.1倍）。很明显，该细胞系中对VRP的抗性是通过与多药耐药细胞系中对阿霉素、长春新碱和秋水仙碱等药物的抗性不同的机制产生的。
