Satyaswaroop P G, Clarke C L, Zaino R J, Mortel R
Department of Obstetrics and Gynecology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Cancer Lett. 1992 Feb 29;62(2):107-14. doi: 10.1016/0304-3835(92)90180-4.
Combined treatment with tamoxifen and progestin effectively controlled human endometrial tumor growth in the nude mouse model. However, after an initial response the tumors became 'resistant' to continuous progestin administration. Tumors excised during the growth arrest or regrowth phases, showed return of the typical growth characteristics of EnCa-101, upon serial transplantation. The characteristic progesterone receptor proteins were observed by Western blot analysis in tamoxifen treated tumors, while tumors treated with both tamoxifen and progestin were devoid of receptor, beginning at 7 days after initiation of progestin therapy. Thus, downregulation of endometrial tumor PR resulting from continuous progestin administration presumably leads to desensitization to progestin, after an initial growth inhibitory response.
在裸鼠模型中，他莫昔芬与孕激素联合治疗可有效控制人子宫内膜肿瘤生长。然而，在初始反应后，肿瘤对持续给予孕激素产生了“抗性”。在生长停滞或再生长阶段切除的肿瘤，经连续传代移植后，显示出EnCa - 101典型的生长特征。通过蛋白质免疫印迹分析在他莫昔芬治疗的肿瘤中观察到特征性的孕激素受体蛋白，而在孕激素治疗开始7天后，同时接受他莫昔芬和孕激素治疗的肿瘤则缺乏受体。因此，持续给予孕激素导致子宫内膜肿瘤孕激素受体下调，可能在初始生长抑制反应后导致对孕激素脱敏。
