Terakawa N, Shimizu I, Ikegami H, Tanizawa O, Matsumoto K
Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.
Cancer. 1988 Apr 1;61(7):1312-5. doi: 10.1002/1097-0142(19880401)61:7<1312::aid-cncr2820610706>3.0.co;2-k.
Effects of 4-hydroxytamoxifen, a major metabolite of tamoxifen, on the proliferation of cancer cells from human endometrial adenocarcinomas obtained by hysterectomy were investigated in primary culture. Competitive binding studies showed that 4-hydroxytamoxifen effectively binds to cytoplasmic estrogen receptors (ER) in uterine adenocarcinomas. Of 20 endometrial adenocarcinomas examined, five tumors were successfully grown in primary cell culture. The addition of 4-hydroxytamoxifen (1 nmol/l to 1 mumol/l) in a medium supplemented with estrogen-free serum resulted in a dose-dependent inhibition of the growth of cancer cells in two tumors having ER. However, 4-hydroxytamoxifen did not affect the growth in the culture system of the remaining three tumors, in which ER were absent in two tumors but were present in one. These results strongly suggest that tamoxifen has a direct growth-inhibitory effect on human endometrial adenocarcinoma possibly through ER in the tumor.
在原代培养中，研究了他莫昔芬的主要代谢产物4-羟基他莫昔芬对通过子宫切除术获得的人子宫内膜腺癌癌细胞增殖的影响。竞争性结合研究表明，4-羟基他莫昔芬能有效结合子宫腺癌中的细胞质雌激素受体（ER）。在检测的20例子宫内膜腺癌中，有5例肿瘤在原代细胞培养中成功生长。在补充无雌激素血清的培养基中添加4-羟基他莫昔芬（1 nmol/l至1 μmol/l），导致具有ER的两个肿瘤中的癌细胞生长受到剂量依赖性抑制。然而，4-羟基他莫昔芬对其余三个肿瘤的培养系统中的生长没有影响，其中两个肿瘤中不存在ER，但有一个肿瘤中存在ER。这些结果强烈表明，他莫昔芬可能通过肿瘤中的ER对人子宫内膜腺癌具有直接的生长抑制作用。
