Dauvois S, Li S M, Martel C, Labrie F
MRC Group in Molecular Endocrinology, Laval University Medical Centre, Quebec, Canada.
Breast Cancer Res Treat. 1989 Dec;14(3):299-306. doi: 10.1007/BF01806301.
Constant release of the androgen 5 alpha-dihydrotestosterone (DHT) in ovariectomized rats bearing DMBA-induced mammary carcinoma caused a marked inhibition of tumor growth induced by 17 beta-estradiol (E2). That DHT acts through interaction with the androgen receptor is supported by the finding that simultaneous treatment with the antiandrogen Flutamide completely prevents DHT action. Particularly illustrative of the potent inhibitory effect of DHT on tumor growth are the decrease by DHT of the number of progressing tumors from 69.2% to 29.2% in E2-treated animals and the increase by DHT of the number of complete responses (disappearance of palpable tumors) from 11.5% to 33.3% in the same groups of animals. The number of new tumors appearing during the 28-day observation period in E2-treated animals decreased from 1.5 +/- 0.3 to 0.7 +/- 0.2 per rat during treatment with DHT, an effect which was also reversed by the antiandrogen Flutamide. The present data demonstrate, for the first time, that androgens are potent inhibitors of DMBA-induced mammary carcinoma growth by an action independent of inhibition of gonadotropin secretion, and suggest an action exerted directly at the tumor level.
在携带二甲基苯并蒽（DMBA）诱导的乳腺癌的去卵巢大鼠中，持续释放雄激素5α-二氢睾酮（DHT）可显著抑制17β-雌二醇（E2）诱导的肿瘤生长。抗雄激素氟他胺同时治疗可完全阻止DHT的作用，这一发现支持了DHT通过与雄激素受体相互作用发挥作用的观点。DHT对肿瘤生长的强大抑制作用特别明显的是，在E2治疗的动物中，DHT使进展期肿瘤的数量从69.2%降至29.2%，并且在同一组动物中，DHT使完全缓解（可触及肿瘤消失）的数量从11.5%增加到33.3%。在E2治疗的动物中，在28天观察期内出现的新肿瘤数量在DHT治疗期间从每只大鼠1.5±0.3降至0.7±0.2，抗雄激素氟他胺也可逆转这一效应。目前的数据首次证明，雄激素是DMBA诱导的乳腺癌生长的有效抑制剂，其作用独立于对促性腺激素分泌的抑制，并提示其作用直接在肿瘤水平发挥。
