Fatty Acid Composition and Metabolism of Tumor Cells Rendered Resistant to the Anticancer Drug Doxorubicin
Fatty Acid Composition and Metabolism of Tumor Cells Rendered Resistant to the Anticancer Drug Doxorubicin
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对抗癌药物阿霉素产生耐药性的肿瘤细胞的脂肪酸组成和代谢
DOI：
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
D. Londos‐Gagliardi
中科院分区：
文献类型：
--
作者：
J. Robert;P. Vrignaud;D. Montaudon;D. Londos‐Gagliardi
蒽环类药物是一类抗癌药物，通过插入DNA碱基对之间发挥作用，从而抑制大分子合成。该系列的主要化合物称为阿霉素或阿霉素，广泛用于治疗血液恶性肿瘤和实体瘤（1）。许多作者已经开发了对阿霉素或其类似物柔红霉素耐药的细胞培养模型（2）。它们中的大多数是通过将细胞连续暴露于药物而获得的，从低毒性浓度开始，然后逐渐增加到非常高的浓度。几乎所有对阿霉素产生耐药性的细胞系都比亲本细胞系掺入了少得多的药物。耐药细胞中药物掺入的这种减少主要是由于药物流出细胞的显著增加，这种流出是主动转运（3）或被动扩散（4）。膜脂可能是重要的耐药现象，无论外排的机制是：要么他们可以干预作为载体的环境和调节其活性，或者他们可以干预调节膜通透性。在Ramu等人的工作中（5），在P388白血病细胞中发现敏感细胞和耐药细胞之间鞘磷脂/磷脂酰胆碱比率存在微小差异，这可能是由于耐药细胞中磷酸胆碱转移酶活性较低所致。然而，本文没有研究这两个品系的脂肪酸组成。研究不同细胞系的作者已经证明耐药细胞的膜流动性降低（6，7），但没有一篇论文提出可能导致膜流动性改变的脂质改变。
Anthracyclines are a family of anticancer drugs acting by intercalation between base pairs of DNA and inhibiting therefore macromolecular synthesis. The main compound of the series is called doxorubicin or adriamycin and is widely used in the treatment of hematological malignancies and solid tumors (1). Numerous authors have developped cell culture models of resistance to doxorubicin or its analogue daunorubicin (2). Most of them are obtained by continuous exposure of the cells to the drug, beginning with low, infratoxic concentrations, which are then progressively increased to very high concentrations. Nearly all the cells lines that have been rendered resistant to doxorubicin incorporate much less amounts of the drug than the parental cell lines. This decrease of drug incorporation in resistant cells is mainly due to a striking increase of drug efflux out of the cell, this efflux being an active transport (3) or a passive diffusion (4). Membrane lipids may be of importance in the phenomenon of resistance, whatever the mechanism of the efflux is : either they may intervene as the environment of the carrier and modulate its activity, or they may intervene in regulating membrane permeability. In a work by Ramu et al. (5) a small difference in the sphingomyelin/phosphatidylcholine ratio between sensitive and resistant cells was noticed in P388 leukemia cells and could be due to a lower phosphocholine transferase activity in resistant cells. The fatty acid composition of the two lines was however not studied in this paper. The membrane fluidity of resistant cells has been shown to decrease by authors working on different cell lines (6, 7) but none of the papers makes a proposal about the lipid modification that could underlie such a modification of membrane fluidity.
膳食诱导酰基链去饱和酶改变大鼠肝细胞质膜的脂质组成和流动性。
影响因子：
2.9
作者：
Storch,J;Schachter,D
通讯作者：
Schachter,D