Jansen G H, Franke H R, Wolbers F, Brinkhuis M, Vermes I
Department of Obstetrics, Twente Hospital Group, Enschede, The Netherlands.
Climacteric. 2008 Aug;11(4):315-21. doi: 10.1080/13697130802232500.
Fulvestrant is an estrogen receptor (ER) antagonist that binds, blocks and degrades the estrogen receptor and is currently used in adjuvant treatment in postmenopausal women with ER-positive breast cancer as an alternative for tamoxifen. As an antagonist, it may induce or aggravate climacteric symptoms. In order to alleviate these symptoms, one could consider hormone therapy. The objective of this study was to analyze the effect of fulvestrant alone or in combination with different steroids in human breast cancer cells in vitro, and to demonstrate whether these steroids will compromise the efficacy of fulvestrant in ER-positive breast cancer cells.
We performed experiments in vitro with various hormone therapy preparations (estradiol (E2), dihydrodydrogesterone (DHD) and tibolone) at a concentration of 10(-6) mol/l alone or combined with fulvestrant in different breast cancer cell lines, ER-positive and ER-negative. After an incubation of 144 h, proliferation and apoptosis were measured. The first was measured by quantification of the expression of cyclin D1 mRNA, the latter by the Nicoletti fragmentation assay.
This in vitro study revealed clear differences in results when various hormone therapy preparations, alone or combined with fulvestrant, are added to ER-positive and ER-negative breast cancer cell lines.
Our study demonstrated that fulvestrant, an ER antagonist used in the treatment of ER-positive breast cancer, combined with E2 and DHD or in combination with tibolone, is not compromised in its efficacy in inducing apoptosis in ER-positive breast cancer cell lines in vitro.
氟维司群是一种雌激素受体（ER）拮抗剂，它能结合、阻断并降解雌激素受体，目前在绝经后雌激素受体阳性乳腺癌患者的辅助治疗中作为他莫昔芬的替代药物使用。作为一种拮抗剂，它可能诱发或加重更年期症状。为了缓解这些症状，可以考虑激素疗法。本研究的目的是分析氟维司群单独使用或与不同甾体类药物联合使用对人乳腺癌细胞的体外作用，并证明这些甾体类药物是否会损害氟维司群对雌激素受体阳性乳腺癌细胞的疗效。
我们在体外对各种激素治疗制剂（雌二醇（E2）、二氢孕酮（DHD）和替勃龙）进行实验，浓度为10（-6）mol/l，单独使用或与氟维司群联合使用，作用于不同的乳腺癌细胞系，包括雌激素受体阳性和阴性细胞系。孵育144小时后，测量细胞增殖和凋亡情况。前者通过细胞周期蛋白D1 mRNA表达的定量来测量，后者通过尼科letti碎片分析法测量。
这项体外研究表明，当各种激素治疗制剂单独或与氟维司群联合添加到雌激素受体阳性和阴性乳腺癌细胞系中时，结果存在明显差异。
我们的研究表明，用于治疗雌激素受体阳性乳腺癌的ER拮抗剂氟维司群，与E2和DHD联合使用或与替勃龙联合使用时，在体外诱导雌激素受体阳性乳腺癌细胞系凋亡的疗效方面不受影响。
