Antimicrotubule effects of estramustine, an antiprostatic tumor drug.
Antimicrotubule effects of estramustine, an antiprostatic tumor drug.
复制标题
雌莫司汀（一种抗前列腺肿瘤药物）的抗微管作用。
作者：
M. Stearns;K. Tew
雌激素[17-β-雌二醇3，N-二(2-氯乙基)氨基甲酸酯；EM]是雌二醇和去氮芥末的稳定结合物，用于治疗前列腺癌。本文研究了EM对体外培养的松鼠色素细胞(红细胞系)和人前列腺癌细胞(DU-145)细胞骨架的影响。光镜和整体电子显微镜研究表明，在微米级(60至120微米)，EM对细胞形状、细胞骨架组织和细胞内运输具有剂量依赖性的破坏作用。去除药物后，EM的细胞学效应在鱼类细胞中迅速可逆，但DU 145S不可逆。免疫荧光研究表明，EM能在鱼类红细胞膜和DU 145细胞中产生微管解体。伴随而来的肌动蛋白微丝阵列的破坏也出现在DU 145细胞中。这些形态数据表明，EM作为一种抗微管药物，与其成分雌二醇：氮芥类相反，具有诱导细胞毒性的作用。观察到的间期细胞微管和细胞基质的破坏在前列腺癌细胞中是不可逆的。EM对细胞骨架的破坏作用最终可能在细胞分裂过程中产生细胞毒性的抗分裂效应。
Estramustine [17 beta-estradiol 3 N bis(2-chloroethyl)carbamate; EM] is a stable conjugate of estradiol and nor-nitrogen mustard that is used for the treatment of human prostatic carcinoma. We have studied the cytotoxic effects of EM on the cytoskeletal organization of squirrelfish pigment cells (erythrophores) and human prostatic tumor cells (DU 145) in culture. Light and whole-mount electron microscopy studies reveal that, at microM levels (60 to 120 microM), EM has a dose-dependent disruptive effect on cell shape, cytoskeletal organization, and intracellular transport. Upon removal of the drug, the cytological effects of EM are rapidly reversible in fish cells but not DU 145s. Immunofluorescent studies reveal that EM produces microtubule disassembly in fish erythrophores and DU 145 cells. A concomitant disruption of actin-microfilament arrays also occurs in DU 145 cells. These morphological data suggest that EM, in contradistinction to its constituent estradiol: nitrogen mustard species, induces cytotoxicity as an antimicrotubule drug. The observed disruption of the microtubules and cytomatrix of interphase cells is not reversible in the prostatic carcinoma cells. The disruptive action of EM on the cytoskeleton could ultimately produce a cytotoxic antimitotic effect in dividing cells.