Verapamil and cyclosporin A potentiate the effects of chemotherapeutic drugs in the human medullary thyroid carcinoma TT cell line not expressing the 170 kDa P-glycoprotein.
The TT-cell line, derived from a patient with metastatic medullary thyroid carcinoma (MTC), was found to exhibit intrinsic resistance to vincristine (VCR) despite the absence of immunohistochemically detectable 170 kDa P-glycoprotein (PGP 170) associated with multidrug resistance (MDR). Verapamil and cyclosporin A, two well known resistance modifiers of MDR, were found to significantly potentiate the action of VCR (60-fold) and to a lesser degree also of VP-16 and daunorubicin (dnr). The present results suggests that resistance of MTC to chemotherapy may be at least partly circumvented by the addition resistance modifiers to chemotherapeutic regimens.
Larsson
R
R
Department of Clinical Pharmacology, University Hospital, Uppsala University, Sweden.
Nygren
P
P
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003524:Cyclosporins / Q000494:pharmacology*; D003630:Daunorubicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004357:Drug Synergism; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology*; D014750:Vincristine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003524:Cyclosporins; D008562:Membrane Glycoproteins; D014750:Vincristine; D005047:Etoposide; D014700:Verapamil; D003630:Daunorubicin