Lee T W, Yang S W, Kim C M, Hong W S, Youn D H
Department of Ophthalmology and Internal Medicine, Korea Cancer Center Hospital, Seoul.
J Korean Med Sci. 1993 Apr;8(2):104-9. doi: 10.3346/jkms.1993.8.2.104.
The chemosensitizing effects of cyclosporin A and verapamil on the cytotoxicity of adriamycin were investigated using MTT assay against two human retinoblastoma cell lines, Y79 and WERI-Rb-1. Y79 and WERI-Rb-1 were totally resistant to doses up to 5.0 micrograms/ml of verapamil. Cyclosporin A inhibited the survival of Y79 and WERI-Rb-1 dose-dependently, however, the maximum inhibition at the highest concentration tested (5.0 micrograms/ml) was less than 50% (% survival at 5.0 micrograms/ml of cyclosporin A: 65.6% and 66.9% in Y79 and WERI-Rb-1, respectively). Combination of cyclosporin A and verapamil did not further inhibit the survival of Y79 and WERI-Rb-1 compared with cyclosporin A alone. Adramycin inhibited the survival of Y79 and WERI-Rb-1 dose-dependently. The chemosensitizing effects of cyclosporin A and verapamil on the cytotoxicity of adriamycin were evaluated in terms of sensitizing index (SI: the ratio of IC50 to adriamycin alone to IC50 to adriamycin in the presence of cyclosporin A and/or verapamil). Cyclosporin A significantly enhanced SI and the addition of verapamil enhanced SI further: SI values at 5.0 micrograms/ml of cyclosporin A, 5.0 micrograms/ml of cyclosporin A plus 1.5 micrograms/ml of cyclosporin A plus 1.5 micrograms/ml of verapamil, 5.0 micrograms/ml of cyclosporin A plus 3.0 micrograms/ml of verapamil were 2.0, 2.6 and 2.8 in Y79 and 2.6, 5.8 and 9.7 in WERI-Rb-1, respectively. These results suggest that cyclosporin A and verapamil are promising chemosensitizers to adriamycin in the treatment of retinoblastoma.
采用MTT法，针对两种人视网膜母细胞瘤细胞系Y79和WERI-Rb-1，研究了环孢素A和维拉帕米对阿霉素细胞毒性的化学增敏作用。Y79和WERI-Rb-1对高达5.0微克/毫升的维拉帕米剂量完全耐药。环孢素A剂量依赖性地抑制Y79和WERI-Rb-1的存活，然而，在测试的最高浓度（5.0微克/毫升）下的最大抑制率小于50%（在5.0微克/毫升环孢素A时的存活率：Y79和WERI-Rb-1分别为65.6%和66.9%）。与单独使用环孢素A相比，环孢素A和维拉帕米联合使用并未进一步抑制Y79和WERI-Rb-1的存活。阿霉素剂量依赖性地抑制Y79和WERI-Rb-1的存活。根据增敏指数（SI：单独阿霉素的IC50与存在环孢素A和/或维拉帕米时阿霉素的IC50之比）评估环孢素A和维拉帕米对阿霉素细胞毒性的化学增敏作用。环孢素A显著提高SI，加入维拉帕米进一步提高SI：在Y79中，5.0微克/毫升环孢素A、5.0微克/毫升环孢素A加1.5微克/毫升维拉帕米、5.0微克/毫升环孢素A加3.0微克/毫升维拉帕米时的SI值分别为2.0、2.6和2.8；在WERI-Rb-1中分别为2.6、5.8和9.7。这些结果表明，环孢素A和维拉帕米在视网膜母细胞瘤治疗中是有前景的阿霉素化学增敏剂。
