Inhibition of cell proliferation and dihydrofolate reductase by liposomes containing methotrexate-dimyristoylphosphatidylethanolamine derivatives and by the glycerophosphorylethanolamine analogs.
作者： Keiichiro Hashimoto , Joan E. Loader , Marcia S. Knight , Stephen C. Kinsky
DOI: 10.1016/0005-2736(85)90405-5
关键词:
摘要: Liposomes, which were prepared with the three methotrexate (MTX)-dimyristoylphosphatidylethanolamine (DMPE) derivatives described in preceding paper, tested for their ability to block proliferation of mouse 3T3 and L1210 cells. Tritiated deoxyuridine incorporation into DNA could be completely inhibited by liposomes sensitized MTX-DMPE I (MTX-gamma-DMPE). Under similar conditions, containing II (MTX-alpha-DMPE) III (MTX-alpha, gamma-diDMPE) produced partial no inhibition, respectively. These effects on cell growth paralleled capacity liposomes, each DMPE derivatives, inhibit dihydrofolate reductase isolated from Analogous experiments corresponding glycerophosphorylethanolamine (glyceroPE) analogs also indicated that MTX-glyceroPE was most effective inhibitor both enzymatic activity. However, apparently enter target cells as a consequence phagocytosis, not via ubiquitous transport system is employed I. For example, novel use thiamine pyrophosphate showed this compound had influence inhibition due whereas antagonize inhibitory The results are discussed reference possible therapeutic advantages these liposomes.
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