Overcoming multidrug resistance in Chinese hamster ovary cells in vitro by cyclosporin A (Sandimmune) and non-immunosuppressive derivatives.
Cyclosporin A (Sandimmune) increased the in vitro susceptibility of 'parental' and 'multidrug-resistant' (MDR) chinese hamster ovary (CHO) cell lines to three anti-tumour drugs: colchicine, daunomycin, and vincristine. Several immunosuppressive or non-immunosuppressive derivatives of cyclosporin (Cs) were compared for their ability to sensitise both parental and MDR cells to chemotherapeutic agents. Although 5-10-fold increases of sensitivity to anti-tumour drugs could be obtained for cells of the parental line with several Cs-derivatives, the largest 'gains' of sensitivity (chemosensitisation) were obtained for the cells of the MDR line and with only some of the Cs derivatives. The MDR cells employed displayed the typical MDR phenotype. However, we found no correlation between the immunosuppressive activity of Cs derivatives and their capacity to reverse MDR and all four possible combinations of these two activities could indeed be shown among the tested Cs derivatives. This study demonstrates for the first time that some immunosuppressive Cs can be devoid of chemosensitising activity.
Gavériaux
C
C
Preclinical Research Department, Sandoz, CH 4002 Basel, Switzerland.
Boesch
D
D
Boelsterli
J J
JJ
Bollinger
P
P
Eberle
M K
MK
Hiestand
P
P
Payne
T
T
Traber
R
R
Wenger
R
R
Loor
F
F
D000818:Animals; D002460:Cell Line; D003078:Colchicine / Q000494:pharmacology; D006224:Cricetinae; D003524:Cyclosporins / Q000494:pharmacology*; D003630:Daunorubicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance; D004357:Drug Synergism; D005260:Female; D006096:Gramicidin / Q000494:pharmacology; D066298:In Vitro Techniques; D008938:Mitosis / Q000187:drug effects; D010053:Ovary / Q000187:drug effects; D014750:Vincristine / Q000494:pharmacology
D003524:Cyclosporins; D006096:Gramicidin; D014750:Vincristine; D003078:Colchicine; D003630:Daunorubicin