Tamoxifen is an antineoplastic nonsteroidal selective estrogen receptor modulator (SERM).

Tamoxifen因其抗雌激素活性(ER)显现出抗肿瘤效果。Tamoxifen对ER的表观亲和力值根据不同ER来源（物种）、蛋白浓度和测定条件。Tamoxifen诱导程序性细胞死亡。[1]Tamoxifen在MCF-7细胞上抑制[3H]胸腺嘧啶掺入和DNA聚合酶活性，并减少培养物中的DNA含量和细胞数量。通过添加雌二醇到培养基中可以迅速逆转Tamoxifen对MCF-7细胞生长的抑制效果。2和6μM Tamoxifen可减少处于S期的细胞比例，增加G1期的细胞数量。在10μM时，Tamoxifen在48小时内引起细胞死亡。[2]Tamoxifen在10天治疗后以约10nM的IC50抑制MCF-7生长。Tamoxifen抑制MCF-7的纤溶酶原激活剂活性，并抑制雌二醇刺激的纤溶酶原激活剂活性。Tamoxifen还引起细胞孕酮受体水平小幅度增加。[3]Tamoxifen能够抑制前列腺癌细胞PC3，PC3-M和DU145的生长（IC50范围为5.5-10μM），这与其抑制蛋白激酶C和诱导p21(waf1/cip1)的表达有关。[4]

在快速生长的雌二醇刺激的MCF-7异种移植瘤之中，Tamoxifen的施用会引起剂量依赖性的肿瘤生长延缓或停滞，显著降低肿瘤细胞在瘤内的增殖。与未经治疗、体积加倍时间为5天、Tpot为2.3天、及%LI为23%的小鼠相比，经Tamoxifen处理的细胞在肿瘤生长放缓（肿瘤加倍时间，12天）、肿瘤潜在加倍时间（Tpot）显著增长（达6.6天）和标记指数（%LI）至第23天后下降至8%。[5] Tamoxifen不仅具有抗雌激素作用，还依赖于物种、组织和基因表现出雌激素特性。它在骨骼和血清脂质浓度方面表现出有利影响，对子宫内膜有促激作用。[1]

Competitive binding assays: Cells are harvested from 150-sq cm T-flasks, and cytosol is prepared at a protein concentration of approximately 2 mg/mL in phosphate buffer. Aliquots of this 180,000 ×g supernatant are then incubated with various concentrations of Tamoxifen and 2.5 nM [3H]estradiol for 16 hr at 0-4 ℃. The free steroids are absorbed by dextran-charcoal [l0 μL of 0.5% Dextran C-5% Norite A in TE buffer] for 1 hr at 0 ℃, and aliquots are counted after centrifugation at 800 ×g, 30 min. The relative binding ability of each competitor is taken as the ratio of the concentration of radioinert estradiol/competitor required to inhibit one-half of the specific [3H]estradiol binding, with the affinity of estradiol set at 100%.

MCF-7 cells are seeded into T-25 flasks (1.5×105 cells/flask) and grown for 2 days in the MEM supplemented with 10 mM HEPES buffer, gentamicin (50 μg/mL), penicillin (100 units/mL), streptomycin (0.1 mg/mL), bovine insulin (6 ng/mL), hydrocortisone (3.75 ng/mL), and 5% calf serum that has been treated with dextran-coated charcoal for 45 min at 55 ℃ to remove endogenous hormones. The medium is then changed to MEM supplemented as described above, except that it contains 2% charcoal dextran-treated calf serum and various concentrations of Tamoxifen. At the end of incubation, cell numbers are counted. (Only for Reference)