Maenpaa J, Wiebe V, Wurz G, Koester S, Emshoff V, Seymour R, DeGregorio M
Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7884.
Cancer Chemother Pharmacol. 1994;35(2):149-52. doi: 10.1007/BF00686638.
To study tamoxifen resistance-stimulated growth, 30 female ovariectomized nude mice were implanted with tamoxifen-resistant tumors and treated with 10-1000 micrograms/day of tamoxifen citrate subcutaneously. Tamoxifen stimulated MCF-7 tumor growth in a dose-dependent manner, with tumoral tamoxifen concentrations increasing proportionally to the dose (1-13 nmol/g), as measured by high-performance liquid chromatography (HPLC). Flow-cytometric analysis revealed that tamoxifen-resistant tumors had a different DNA content as compared with wild-type MCF-7 cells. In contrast to earlier results, these data suggest that tamoxifen resistance-stimulated growth is associated with increasing rather than decreasing tumoral tamoxifen concentrations. Furthermore, the observed ploidy changes in the tamoxifen-resistant tumors imply that a genetic basis may exist for the development of tamoxifen resistance.
为研究他莫昔芬耐药性刺激的生长情况，30只雌性去卵巢裸鼠被植入他莫昔芬耐药肿瘤，并皮下注射每日10 - 1000微克的枸橼酸他莫昔芬进行治疗。他莫昔芬以剂量依赖的方式刺激MCF - 7肿瘤生长，通过高效液相色谱法（HPLC）测定，肿瘤中他莫昔芬浓度与剂量成比例增加（1 - 13纳摩尔/克）。流式细胞术分析显示，与野生型MCF - 7细胞相比，他莫昔芬耐药肿瘤的DNA含量不同。与早期结果相反，这些数据表明，他莫昔芬耐药性刺激的生长与肿瘤中他莫昔芬浓度的增加而非减少有关。此外，在他莫昔芬耐药肿瘤中观察到的倍性变化意味着他莫昔芬耐药性的发展可能存在遗传基础。
