Methotrexate differentially affects growth of suspension and adherent cells
Methotrexate differentially affects growth of suspension and adherent cells
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DOI：
10.1016/j.biocel.2003.09.002
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发表时间：
2004-05-01
影响因子：
4
通讯作者：
Igarashi, K
中科院分区：
文献类型：
--
作者：
Kimura, E;Nishimura, K;Igarashi, K
比较低浓度甲氨蝶呤（MTX）对悬浮细胞（FM 3A、2134和THP-1）和贴壁细胞（NIH 3 T3和V79）生长的影响。引起细胞生长抑制的甲氨蝶呤浓度在悬浮细胞中低于贴壁细胞。FM 3A、2134、THP-1、NIH 3 T3和V79细胞的IC 50分别为3.5、5、9、30和50 nM。细胞生长的抑制被四氢叶酸完全逆转，并被腺苷和胸苷完全或显著逆转，表明低浓度甲氨蝶呤的作用是由于抑制嘌呤和嘧啶的生物合成。在悬浮细胞中，但不是在贴壁细胞中，甲氨蝶呤治疗后的S-腺苷甲硫氨酸和多胺的水平下降。用S-腺苷甲硫氨酸处理后，悬浮细胞的生长而非贴壁细胞的生长显著恢复。然而，亚精胺治疗没有逆转甲氨蝶呤在任何细胞系中的作用。甲氨蝶呤在悬浮细胞与贴壁细胞中的优先抑制作用主要是由于甲氨蝶呤的更快速摄取。这可能与低剂量甲氨蝶呤的体内效应有关，因为淋巴细胞是悬浮细胞，所以甲氨蝶呤具有免疫抑制和抗炎作用。(C)2003爱思唯尔有限公司。保留所有权利。
The effects of low concentrations of methotrexate (MTX) on the growth of suspension (FM3A, 2134 and THP-1) and adherent (NIH3T3 and V79) cells were compared. The concentration of methotrexate to cause the inhibition of cell growth was lower in suspension cells than in adherent cells. The IC50 for FM3A, 2134, THP-1, NIH3T3 and V79 cells were 3.5, 5, 9, 30 and 50 nM, respectively. The inhibition of cell growth was reversed completely by tetrahydrofolate and was fully or significantly reversed by adenosine and thymidine, suggesting that the effects of low concentrations of methotrexate result from the inhibition of biosynthesis of purines and pyrimidines. In suspension cells but not in adherent cells there was a decrease in the levels of S-adenosylmethionine and polyamines after methotrexate treatment. Growth of suspension but not adherent cells was significantly recovered by treatment with S-adenosylmethionine. However, treatment with spermidine did not reverse the effects of methotrexate in any of the cell lines. The preferential inhibitory effect of methotrexate in suspension cells versus adherent cells was due mainly to a more rapid uptake of methotrexate. This may be relevant to the in vivo effects of low doses of methotrexate, which, have immunosuppressive and anti-inflammatory effects, because lymphocytes are suspension cells. (C) 2003 Elsevier Ltd. All rights reserved.