Maenpaa J U, Wurz G T, Baker W J, Wiebe V J, Emshoff V D, Koester S K, Seymour R C, Koehler R E, DeGregorio M W
Department of Medicine/Oncology, UTHSCSA, San Antonio, TX 78284-7884.
Oncol Res. 1993;5(12):461-6.
The in vivo growth rate and the chemosensitivity patterns of a cell clone selected by tamoxifen from the estrogen receptor-negative human breast cancer cell line MDA-MB-231 was studied in the nude mouse model and with flow cytometry. To investigate the growth rate of the wild-type and clone cells in vivo, the cells were inoculated into the opposite flanks of 5 male nude mice. Drug sensitivity to doxorubicin (10 ng/mL), vinblastine (1 ng/mL), and paclitaxel (1 ng/mL) was examined in wild-type/clone cell mixture using flow cytometry. Northern blot technique was used to study the expression of mdr-1 messenger RNA in both the wild-type and the clone cells. The tumors derived from the clone and wild-type cells were, following a 3-week growth period, 260.2 +/- 78.8 mm2 vs. 68.3 +/- 50.8 mm2 in size, respectively (P < 0.001). Following a 28-day continuous exposure, doxorubicin was selectively, toxic to the wild-type cells, while having no apparent effect on the clone population. However, paclitaxel- and vinblastine-treated wild-type/clone cell mixtures did not exhibit a differential cytotoxic effect on either cell population. It was concluded that the clone selected by tamoxifen shows an aggressive growth rate in vivo and an altered chemosensitivity pattern to doxorubicin in vitro.
在裸鼠模型中并通过流式细胞术，研究了从雌激素受体阴性的人乳腺癌细胞系MDA-MB-231中经他莫昔芬筛选出的细胞克隆的体内生长速率和化学敏感性模式。为了研究野生型和克隆细胞在体内的生长速率，将细胞接种到5只雄性裸鼠的双侧胁腹。使用流式细胞术检测野生型/克隆细胞混合物对阿霉素（10 ng/mL）、长春碱（1 ng/mL）和紫杉醇（1 ng/mL）的药物敏感性。采用Northern印迹技术研究野生型和克隆细胞中mdr-1信使核糖核酸的表达。在3周的生长期后，源自克隆细胞和野生型细胞的肿瘤大小分别为260.2±78.8 mm²和68.3±50.8 mm²（P<0.001）。连续暴露28天后，阿霉素对野生型细胞有选择性毒性，而对克隆细胞群体无明显影响。然而，紫杉醇和长春碱处理的野生型/克隆细胞混合物对两种细胞群体均未表现出不同的细胞毒性作用。得出的结论是，经他莫昔芬筛选出的克隆在体内显示出侵袭性生长速率，在体外对阿霉素的化学敏感性模式发生改变。
