Arafah B M, Griffin P, Gordon N H, Pearson O H
Cancer Res. 1986 Jul;46(7):3268-72.
Cells obtained from freshly resected human breast cancer were grown in vitro utilizing the soft agar technique. The effects of adding an antiestrogen (tamoxifen, TAM) and 17 beta-estradiol alone or simultaneously on cell growth were assessed. The addition of TAM (10(-6) M) to the medium resulted in a significant decrease in cell growth in 26 of 36 (72%) estrogen receptor (ER)-positive tumors and in one of 5 ER-negative tumors (20%). The degree of inhibition caused by TAM was significantly higher in the ER-positive tumors that also contain the progesterone receptor (PgR) as compared to those that lacked that receptor (i.e., PgR negative) (46.2 +/- 2% versus 36.2 +/- 1.2% inhibition, P less than 0.01). The simultaneous addition of 17 beta-estradiol (10(-8) M) neutralized the inhibitory effect of TAM (10(-6) M) in the majority of tumors. With the presence of serum in the medium, the addition of 17 beta-estradiol alone resulted in an enhancement of cell growth in 6 of 17 tumors. However, because of the confounding effects of serum in the medium, we studied the individual effect of 17 beta-estradiol (10(-8) M) when added alone under serum-free conditions. Of 20 tumors studied, 17 beta-estradiol significantly enhanced cell growth in 12. There was a 67.8 +/- 12.6% increase in the number of colonies formed in these 12 responding tumors. One of these 12 responding tumors was ER negative as well as PgR negative, while the rest were all ER positive. These in vitro studies demonstrate that this approach can provide valuable information on endocrine mechanisms controlling the growth of human breast cancer.
利用软琼脂技术在体外培养从新鲜切除的人类乳腺癌中获取的细胞。评估单独添加抗雌激素药物（他莫昔芬，TAM）和17β - 雌二醇或同时添加二者对细胞生长的影响。向培养基中添加TAM（10⁻⁶ M）导致36个雌激素受体（ER）阳性肿瘤中的26个（72%）以及5个ER阴性肿瘤中的1个（20%）细胞生长显著减少。与缺乏孕激素受体（PgR）（即PgR阴性）的ER阳性肿瘤相比，同时含有PgR的ER阳性肿瘤中TAM引起的抑制程度显著更高（抑制率分别为46.2 ± 2%和36.2 ± 1.2%，P < 0.01）。同时添加17β - 雌二醇（10⁻⁸ M）可中和TAM（10⁻⁶ M）在大多数肿瘤中的抑制作用。在培养基中有血清存在的情况下，单独添加17β - 雌二醇导致17个肿瘤中的6个细胞生长增强。然而，由于培养基中血清的混杂效应，我们研究了在无血清条件下单独添加17β - 雌二醇（10⁻⁸ M）的个体效应。在研究的20个肿瘤中，17β - 雌二醇使12个肿瘤的细胞生长显著增强。这12个有反应的肿瘤中形成的集落数量增加了67.8 ± 12.6%。这12个有反应的肿瘤中有1个同时为ER阴性和PgR阴性，其余均为ER阳性。这些体外研究表明，这种方法可为控制人类乳腺癌生长的内分泌机制提供有价值的信息。
