Villalobos M, Aranda M, Nuñez M I, Becerra D, Olea N, Ruiz de Almodovar M, Pedraza V
Department of Radiology, School of Medicine, University of Granada, Spain.
Acta Oncol. 1995;34(3):413-7. doi: 10.3109/02841869509094000.
MCF7 human breast cancer cells growing as multicellular spheroids were examined as a model of three-dimensional cellular organization. Estrogen-free medium inhibited spheroid formation. In medium containing estrogens, the antiestrogen hydroxytamoxifen decreased the spheroid growth rate. Analyses with the recursion formula after Gompertz fitting showed that the rate of exponential decrease in growth rate (alpha) was alpha 0.099 +/- 0.013 d-1, and the decrease in alpha' was 0.061 +/- 0.015 d-1 for 0.1 microM hydroxytamoxifen and control spheroids respectively. MCF7 cells which had been growth arrested in an estrogen-free medium showed a significant decrease in radiosensitivity (surviving fraction at 2 Gy, SF2 = 63%) when compared with 0.1 nM 17 beta-estradiol-treated cells (SF2 = 38%). No differences in radiosensitivity were seen in MCF7 spheroids in estrogen-supplemented medium (radiation dose necessary to control 50% of spheroids (SCD50) was 5.51 Gy; derived alpha, beta and SF2 were 0.301 +/- 0.110 Gy-1, 0.018 +/- 0.005 Gy-2, and 51% respectively) when compared with monolayer cultures in the same medium (alpha = 0.316 +/- 0.059 Gy-1, beta = 0.023 +/- 0.006 Gy-2 and SF2 = 50%). In the spheroid model, manipulating the cellular environment, i.e., with estrogen treatment, modulates sensitivity to ionizing radiation.
以呈多细胞球体生长的MCF7人乳腺癌细胞作为三维细胞组织模型进行研究。无雌激素培养基可抑制球体形成。在含有雌激素的培养基中，抗雌激素药物羟基他莫昔芬可降低球体生长速率。经Gompertz拟合后用递归公式分析表明，对于0.1μM羟基他莫昔芬处理的球体和对照球体，生长速率的指数下降率（α）分别为0.099±0.013 d⁻¹和0.061±0.015 d⁻¹。与用0.1 nM 17β-雌二醇处理的细胞（存活分数在2 Gy时，SF2 = 38%）相比，在无雌激素培养基中生长停滞的MCF7细胞的放射敏感性显著降低（在2 Gy时的存活分数，SF2 = 63%）。在补充雌激素的培养基中，MCF7球体的放射敏感性与相同培养基中的单层培养物相比无差异（控制50%球体所需的辐射剂量（SCD50）为5.51 Gy；推导的α、β和SF2分别为0.301±0.110 Gy⁻¹、0.018±0.005 Gy⁻²和51%）（α = 0.316±0.059 Gy⁻¹，β = 0.023±0.006 Gy⁻²，SF2 = 50%）。在球体模型中，通过雌激素处理等方式操纵细胞环境可调节对电离辐射的敏感性。
