Suto A, Bradlow H L, Kubota T, Kitajima M, Wong G Y, Osborne M P, Telang N T
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Steroids. 1993 May;58(5):215-9. doi: 10.1016/0039-128x(93)90021-e.
The experiments performed in this study were designed to establish that (1) acquisition of anchorage-independent growth, a biological characteristic of tumorigenically transformed phenotype, can be modulated by prototypic tumor-suppressing agents, and (2) modulation of growth is influenced by the metabolic competence of the cells to biotransform estradiol, MCF-7 human breast carcinoma cells exhibited linear cell proliferative kinetics with a 41-hour population doubling time, and a 15% colony-forming efficiency in 0.33% agar. Indole-3-carbinol (13C), a naturally occurring tumor-suppressive agent; tamoxifen (TAM), an antiestrogenic agent; and 4-hydroxytamoxifen (4-OHTAM), a metabolite of TAM, demonstrated 73.7%, 72.5%, and 89.9% suppression in anchorage-independent growth of MCF-7 cells, respectively. At the metabolic level, 13C and 4-OHTAM induced 2.3-fold (P < 0.0001) and 1.3-fold increase (P = 0.001) relative to their own controls in the extent of 2-hydroxylation of estradiol. The results indicate that growth inhibition by 13C, TAM, and 4-OHTAM may in part be due to altered estradiol metabolism in MCF-7 cells. Thus, anchorage-independent growth and altered biotransformation of estradiol may constitute useful cellular and endocrine markers to evaluate the biological response of chemosuppressive agents.
（1）获得不依赖贴壁生长这一致瘤性转化表型的生物学特性，可受到典型肿瘤抑制因子的调节；（2）生长调节受细胞将雌二醇进行生物转化的代谢能力影响。MCF-7人乳腺癌细胞表现出线性细胞增殖动力学，群体倍增时间为41小时，在0.33%琼脂中的集落形成效率为15%。吲哚-3-甲醇（13C），一种天然存在的肿瘤抑制因子；他莫昔芬（TAM），一种抗雌激素药物；以及4-羟基他莫昔芬（4-OHTAM），TAM的一种代谢产物，分别在MCF-7细胞的不依赖贴壁生长中显示出73.7%、72.5%和89.9%的抑制率。在代谢水平上，相对于各自的对照，13C和4-OHTAM使雌二醇2-羟化程度分别增加了2.3倍（P < 0.0001）和1.3倍（P = 0.001）。结果表明，13C、TAM和4-OHTAM对生长的抑制可能部分归因于MCF-7细胞中雌二醇代谢的改变。因此，不依赖贴壁生长和雌二醇生物转化的改变可能构成评估化学抑制因子生物学反应的有用细胞和内分泌标志物。
