Abstract
Membrane transport characteristics of the folate analogue methotrexate (MTX) were studied in a human squamous carcinoma cell line of the head and neck (HNSCC) adapted to grow in tissue culture media with nanomolar reduced folate concentrations (SCC-11B-LF), as compared to SCC-11B cells grown in standard medium containing high folate concentrations. We observed that SCC-11B-LF cells exhibited a 10.5-fold increased uptake of [3H]-MTX via the reduced folate/MTX carrier system compared to SCC-11B cells. Affinity labelling of the reduced folate/MTX carrier system suggests that the up-regulation of [3H]-MTX transport mainly results from an increased rate of carrier translocation, and only to a minor extent (15-20%) from an increased amount of carrier protein. The upregulation of MTX transport resulted in a 2.4-fold increased growth inhibitory effect by MTX. These results suggest that membrane transport may play a more important role in MTX-cytotoxicity when SCC-11B cells in vitro are grown in more physiological folate concentrations.
Original language | English |
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Pages (from-to) | 1265-8 |
Number of pages | 4 |
Journal | Anticancer research |
Volume | 11 |
Issue number | 3 |
Publication status | Published - 1 May 1991 |
Keywords
- Adaptation, Physiological
- Biological Transport
- Carcinoma, Squamous Cell/metabolism
- Cell Membrane/metabolism
- Folic Acid/pharmacokinetics
- Head and Neck Neoplasms/metabolism
- Humans
- Methotrexate/pharmacokinetics
- Tumor Cells, Cultured/drug effects
- Up-Regulation