Suh Nanjoo, Lamph William W, Glasebrook Andrew L, Grese Timothy A, Palkowitz Alan D, Williams Charlotte R, Risingsong Renee, Farris M Rendi, Heyman Richard A, Sporn Michael B
Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Clin Cancer Res. 2002 Oct;8(10):3270-5.
The selective estrogen receptor modulator arzoxifene and the rexinoid LG 100268 were active not only as single agents for prevention and treatment of breast cancer in the rat model that uses nitrosomethylurea as the carcinogen but also showed striking synergy, both preventively and therapeutically, in a series of six experiments with a total of 465 rats. Mechanistic studies in cell culture reported here suggest that enhancement of stromal-epithelial interactions may contribute to this synergy. The possible clinical use of the combination of arzoxifene and LG 100268 for prevention of breast cancer in women at high risk, for treatment of women in the adjuvant setting, or for treatment of end-stage disease should now be considered.
选择性雌激素受体调节剂阿佐昔芬和视黄酸X受体激动剂LG 100268不仅在以亚硝基甲基脲作为致癌物的大鼠乳腺癌预防和治疗模型中作为单一药物具有活性，而且在一系列共465只大鼠的六个实验中，无论在预防还是治疗方面均显示出显著的协同作用。本文报道的细胞培养机制研究表明，基质-上皮相互作用的增强可能促成了这种协同作用。现在应该考虑阿佐昔芬和LG 100268联合用药在高危女性乳腺癌预防、辅助治疗或晚期疾病治疗中的潜在临床应用。
