RRC ID 41663
著者 Akutsu M, Furukawa Y, Tsunoda S, Izumi T, Ohmine K, Kano Y.
タイトル Schedule-dependent synergism and antagonism between methotrexate and cytarabine against human leukemia cell lines in vitro.
ジャーナル Leukemia
Abstract Methotrexate (MTX) and cytarabine have been widely used for the treatment of acute leukemias and lymphomas for over 30 years. However, the optimal schedule of this combination is yet to be determined and a variety of schedules of the combination has been used. We studied the cytotoxic effects of MTX and cytarabine in combination against human leukemia cell lines at various schedules in vitro. The effects of the combinations at the concentration of drug that produced 80% cell growth inhibition (IC(80)) were analyzed using the isobologram method of Steel and Peckham. Simultaneous exposure to MTX and cytarabine for 3 days produced antagonistic effects in human T cell leukemia, MOLT-3 and CCRF-CEM, B cell leukemia, BALL-1, Burkitt's lymphoma, Daudi, promyelocytic leukemia, HL-60 and Philadelphia chromosome-positive leukemia, K-562 cells. Simultaneous exposure to MTX and cytarabine for 24 h produced antagonistic effects, sequential exposure to MTX for 24 h followed by cytarabine for 24 h produced synergistic effects, and the reverse sequence produced additive effects in both CCRF-CEM and HL-60 cells. Sequential exposure to MTX for 24 h followed by cytarabine for 3 days also produced synergistic effects in MOLT-3 cells. Cell cycle analysis supported these observations. Our findings suggest that the simultaneous administration of MTX and cytarabine is not appropriate and the sequential administration of MTX followed by cytarabine may be the optimal schedule of this combination.
巻・号 16(9)
ページ 1808-17
公開日 2002-9-1
DOI 10.1038/sj.leu.2402573
PMID 12200697
MeSH Antineoplastic Combined Chemotherapy Protocols / administration & dosage* Cell Cycle / drug effects Cytarabine / administration & dosage Cytarabine / antagonists & inhibitors Cytarabine / pharmacology* Dose-Response Relationship, Drug Drug Administration Schedule Drug Screening Assays, Antitumor Drug Synergism Humans Leukemia / drug therapy* Methotrexate / administration & dosage Methotrexate / antagonists & inhibitors Methotrexate / pharmacology* Tetrazolium Salts Thiazoles Tumor Cells, Cultured / drug effects*
IF 8.665
引用数 20
WOS 分野 HEMATOLOGY ONCOLOGY
リソース情報
ヒト・動物細胞 BALL-1(RCB0256)