title: Methotrexate-induced resistance to dactinomycin in choriocarcinoma.
abstract: NaUCC-2, a choriocarcinoma cell line, was derived from a patient who had a very poor clinical response to combination chemotherapy. Methotrexate (MTX) might have inhibited the antitumor effect of dactinomycin. To investigate this point, in vitro studies were performed to determine the sensitivity and uptake of MTX and dactinomycin (administered individually and in combination) to NaUCC-2 and three other choriocarcinoma cell lines. Dihydrofolate reductase (DHFR) concentrations were studied as well. Although NaUCC-2 showed sensitivity to MTX and dactinomycin, which were comparable to the other cell lines when they were given separately, NaUCC-2 was unique in that the combination of MTX and dactinomycin was less lethal than dactinomycin given by itself. The uptake of MTX in NaUCC-2 was significantly higher than that in the other cell lines, and MTX also induced an increase in dactinomycin uptake in NaUCC-2. There was no significant difference in DHFR activity. Although additional studies are necessary to determine the mechanism responsible for this effect, these findings suggest that a mechanism other than drug uptake or DHFR activity must play a role in the drug resistance for choriocarcinoma. These findings also suggest that the most commonly used combination chemotherapy for choriocarcinoma, dactinomycin and MTX, may not always be the best method.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Nagoya University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Goto
authors.forename: Y
authors.initials: Y
authors.lastname: Okayama
authors.forename: C
authors.initials: C
authors.lastname: Fan
authors.forename: S
authors.initials: S
authors.lastname: Ueda
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.forename: Y
authors.initials: Y
authors.lastname: Furuhashi
authors.forename: T
authors.initials: T
authors.lastname: Ishizuka
authors.forename: Y
authors.initials: Y
authors.lastname: Tomoda
mesh_terms: D000328:Adult; D000782:Aneuploidy; D000971:Antineoplastic Combined Chemotherapy Protocols; D001692:Biological Transport; D002822:Choriocarcinoma / Q000188:drug therapy* / Q000235:genetics; D003609:Dactinomycin / Q000008:administration & dosage / Q000378:metabolism; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage* / Q000378:metabolism; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D003609:Dactinomycin; D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate