Jordan V C, Allen K E, Dix C J
Cancer Treat Rep. 1980 Jun-Jul;64(6-7):745-59.
This paper reviews the recent laboratory findings about the nonsteroidal antiestrogen, tamoxifen, and its more potent major metabolite, monohydroxytamoxifen. Both compounds stimulate progesterone receptor synthesis in the rat uterus, and there is an inhibition of cell division in the uterine luminal epithelial cells. The effects of tamoxifen in vivo may be a result of the net effects of the parent compound and monohydroxytamoxifen. In rats with dimethylbenzanthracene (DMBA)-induced rat mammary carcinomata, young tumors that are estrogen receptor- and progesterone receptor-rich respond more favorably to tamoxifen that do older estrogen receptor- and progesterone receptor-poor tumors. However, the antitumor effect of tamoxifen in the DMBA-induced rat mammary carcinoma model is probably a result of the blockade of tumor estrogen receptors, a reduction in circulating gonadotropins, lower circulating estrogen levels, and lower circulating prolactin levels. The 30-days treatment of rats with tamoxifen 30 days after DMBA resulted in a dose-related decrease in the appearance and numbers of mammary tumors; however, only continuous therapy maintained animals in a tumor-free state. Monohydroxytamoxifen was a less-potent antitumor agent, probably because it is cleared from the rat more rapidly than tamoxifen. The present laboratory findings support the clinical use of tamoxifen as a treatment of endometrial carcinoma and the resultant metastases and as an adjuvant therapy after surgery for breast cancer.
本文综述了关于非甾体类抗雌激素药物他莫昔芬及其更具活性的主要代谢产物单羟基他莫昔芬的近期实验室研究结果。这两种化合物均可刺激大鼠子宫中孕激素受体的合成，并抑制子宫腔上皮细胞的细胞分裂。他莫昔芬在体内的作用可能是母体化合物和单羟基他莫昔芬净效应的结果。在二甲基苯并蒽（DMBA）诱导的大鼠乳腺癌模型中，富含雌激素受体和孕激素受体的年轻肿瘤对他莫昔芬的反应比雌激素受体和孕激素受体含量较低的老年肿瘤更有利。然而，他莫昔芬在DMBA诱导的大鼠乳腺癌模型中的抗肿瘤作用可能是由于肿瘤雌激素受体的阻断、循环促性腺激素的减少、循环雌激素水平的降低以及循环催乳素水平的降低。在DMBA处理30天后用他莫昔芬对大鼠进行30天的治疗，可导致乳腺肿瘤的出现和数量呈剂量相关的减少；然而，只有持续治疗才能使动物保持无瘤状态。单羟基他莫昔芬是一种活性较低的抗肿瘤药物，可能是因为它比他莫昔芬从大鼠体内清除得更快。目前的实验室研究结果支持他莫昔芬作为子宫内膜癌及其转移灶的治疗药物以及乳腺癌手术后辅助治疗药物的临床应用。
