Kawamura I, Mizota T, Mukumoto S, Manda T, Masuda K, Nakamura T, Kubota H, Matsumoto S, Nishigaki F, Shimomura K
Department of Pharmacology, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Arzneimittelforschung. 1989 Aug;39(8):889-93.
The pharmacological effects of droloxifene [E)-a [p-[2-(dimethylamino)ethoxy]phenyl]-a'-ethyl-3-stilbenol, FK435), a new antiestrogen drug, were studied and compared with those of tamoxifen in animals and in vitro cultured cells. Droloxifene showed about 20-fold and 3-fold higher affinity to estrogen receptors (ER) in the rat uterus and human ER positive MCF-7 breast carcinoma cells, respectively, than tamoxifen, and was more active in decreasing uterine weight of mature rats and 17 beta-estradiol-treated immature rats. Tamoxifen increased uterus growth in immature rats, but droloxifene did not, suggesting that droloxifene has no estrogenic effects. Both drugs inhibited the growth of in vitro cultured MCF-7 cells, with droloxifene being the more active agent, but this effect of both drugs was countered by 17 beta-estradiol. Neither drug, however, had effects on the in vitro growth of human ER negative MDA-MB-231 breast carcinoma cells. In vivo, both drugs inhibited the growth of MCF-7 carcinoma implanted subcutaneously in BALB/c nu/nu mice, but not the growth of human ER negative MX-1 breast carcinoma. The results suggest that droloxifene has antitumor effects on human ER positive breast cancers, and would be useful for the treatment of estrogen-dependent breast cancers.
对新型抗雌激素药物屈洛昔芬[（E）-α-[对-[2-（二甲氨基）乙氧基]苯基]-α'-乙基-3-二苯乙烯醇，FK435]的药理作用进行了研究，并在动物和体外培养细胞中与他莫昔芬的药理作用进行了比较。屈洛昔芬对大鼠子宫和人雌激素受体（ER）阳性的MCF-7乳腺癌细胞中雌激素受体的亲和力分别比他莫昔芬高约20倍和3倍，并且在降低成熟大鼠和经17β-雌二醇处理的未成熟大鼠子宫重量方面更具活性。他莫昔芬可使未成熟大鼠子宫生长增加，但屈洛昔芬则不会，这表明屈洛昔芬没有雌激素样作用。两种药物均抑制体外培养的MCF-7细胞的生长，屈洛昔芬的活性更强，但两种药物的这种作用均被17β-雌二醇抵消。然而，两种药物对人ER阴性的MDA-MB-231乳腺癌细胞的体外生长均无影响。在体内，两种药物均抑制皮下接种于BALB/c nu/nu小鼠的MCF-7癌的生长，但不抑制人ER阴性的MX-1乳腺癌的生长。结果表明，屈洛昔芬对人ER阳性乳腺癌具有抗肿瘤作用，可用于治疗雌激素依赖性乳腺癌。
