Steube K G, Grunicke D, Pietsch T, Gignac S M, Pettit G R, Drexler H G
German Collection of Microorganisms and Cell Cultures (DSM), Department of Human and Animal Cell Cultures, Braunschweig.
Leukemia. 1992 Oct;6(10):1048-53.
The effects of two natural peptides, dolastatin 10 and dolastatin 15, on growth and differentiation of hematopoietic cells were studied using freshly explanted leukemia cells and continuous leukemia cell lines. The proliferation of several myeloid cell lines and of growth-factor-stimulated peripheral blood cells from patients with acute myeloid leukemia (AML) was efficiently inhibited by the two agents at concentrations between 1 and 0.01 nM. Growth inhibition was dose-dependent and reversible. Neither of the dolastatins exhibited significant cytotoxicity on dividing cells, nor did they interfere with the viability of resting cells. The 12-O-tetradecanoylphorbol 13-acetate or bryostatin I induced differentiation of AML cells was not affected by the dolastatins. Short-term exposure to the phorbol ester conferred reduced sensitivity of the cell line HL-60 to the antiproliferative effect of the drugs. Our data suggest that the dolastatins alone or in combination with other drugs could exert a role in the treatment of human myeloid leukemia.
利用新鲜分离的白血病细胞和连续白血病细胞系，研究了两种天然肽——多拉司他汀10和多拉司他汀15对造血细胞生长和分化的影响。两种药物在1至0.01 nM的浓度下，可有效抑制几种髓系细胞系以及急性髓系白血病（AML）患者经生长因子刺激的外周血细胞的增殖。生长抑制呈剂量依赖性且可逆。两种多拉司他汀对分裂细胞均未表现出明显的细胞毒性，也不干扰静止细胞的活力。12 - O - 十四酰佛波醇13 - 乙酸酯或苔藓抑素I诱导的AML细胞分化不受多拉司他汀影响。短期暴露于佛波酯会使HL - 60细胞系对药物的抗增殖作用敏感性降低。我们的数据表明，多拉司他汀单独使用或与其他药物联合使用可能在人类髓系白血病的治疗中发挥作用。
