Kangas L, Nieminen A L, Blanco G, Grönroos M, Kallio S, Karjalainen A, Perilä M, Södervall M, Toivola R
Cancer Chemother Pharmacol. 1986;17(2):109-13. doi: 10.1007/BF00306737.
The antitumor effects of a new antiestrogen, Fc-1157a have been studied in vitro and in vivo. In vitro the effect of Fc-1157a was comparable to that of tamoxifen. The effect was dose-dependent, and at concentrations higher than 10(-6) mol/1 Fc-1157a induced real cell death of the MCF-7 cells. In DMBA-induced mammary cancer in rats Fc-1157a decreased the number of new tumors and inhibited the growth of existing tumors, these effects being statistically highly significant. The ratio of growing tumors to stable and regressing tumors was significantly decreased. Although these effects were slightly stronger with Fc-1157a than with tamoxifen, the difference between these two compounds was not statistically significant. Murine uterine sarcoma, an estrogen receptor-negative tumor, was resistant to tamoxifen, but was statistically significantly inhibited by high doses (100 and 200 mg/kg-1 day-1 for 5 days) of Fc-1157a. The antitumor effects of Fc-1157a are due mainly to the antiestrogenic activity. At high concentrations in vitro and at high doses in vivo Fc-1157a exerts antitumor effects some of which are different from those of tamoxifen and are directed even against estrogen receptor-negative tumors. The exact mechanism of the observed cytolytic effect at high doses is unknown.
一种新型抗雌激素药物Fc - 1157a的抗肿瘤作用已在体外和体内进行了研究。在体外，Fc - 1157a的作用与他莫昔芬相当。其作用呈剂量依赖性，当浓度高于10(-6) mol/1时，Fc - 1157a可诱导MCF - 7细胞发生真正的细胞死亡。在二甲基苯并蒽（DMBA）诱导的大鼠乳腺癌模型中，Fc - 1157a减少了新肿瘤的数量，并抑制了现有肿瘤的生长，这些作用在统计学上具有高度显著性。生长中的肿瘤与稳定和消退肿瘤的比例显著降低。尽管Fc - 1157a的这些作用比他莫昔芬略强，但这两种化合物之间的差异在统计学上并不显著。小鼠子宫肉瘤是一种雌激素受体阴性肿瘤，对他莫昔芬耐药，但高剂量（100和200 mg/kg - 1天 - 1，共5天）的Fc - 1157a对其有统计学上的显著抑制作用。Fc - 1157a的抗肿瘤作用主要归因于其抗雌激素活性。在体外高浓度和体内高剂量时，Fc - 1157a发挥抗肿瘤作用，其中一些作用与他莫昔芬不同，甚至针对雌激素受体阴性肿瘤。高剂量下观察到的细胞溶解作用的确切机制尚不清楚。
