Chemosensitization to adriamycin by cyclosporin A and verapamil in human retinoblastoma cell lines.
10.3346/jkms.1993.8.2.104
- Author:
Tai Won LEE
1
;
Sung Wook YANG
;
Chang Min KIM
;
Weon Seon HONG
;
Dong Ho YOUN
Author Information
1. Department of Ophthalmology and Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Chemosensitization;
Adriamycin;
Cyclosporin A;
Verapamil;
Retinoblastoma cell lines
- MeSH:
Cell Survival/drug effects;
Cyclosporine/*pharmacology;
Doxorubicin/*pharmacology;
Eye Neoplasms/drug therapy/*pathology;
Humans;
Retinoblastoma/drug therapy/*pathology;
Tumor Cells, Cultured;
Verapamil/*pharmacology
- From:Journal of Korean Medical Science
1993;8(2):104-109
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
