Selective inhibition of 17β-hydroxysteroid dehydrogenase type 1 (17βHSD1) reduces estrogen responsive cell growth of T47-D breast cancer cells
Selective inhibition of 17β-hydroxysteroid dehydrogenase type 1 (17βHSD1) reduces estrogen responsive cell growth of T47-D breast cancer cells
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DOI：
10.1016/j.jsbmb.2009.02.006
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发表时间：
2009-04-01
影响因子：
4.1
通讯作者：
Hartmann, Rolf W.
中科院分区：
文献类型：
--
作者：
Kruchten, Patricia;Werth, Ruth;Hartmann, Rolf W.
最强的雌激素雌二醇（E2）在雌激素依赖性疾病的发生和发展中起着关键作用。17 β-羟类固醇脱氢酶1型（17 β HSD 1）催化雌酮（E1）形成NADPH依赖性E2。它通常在乳腺癌和子宫内膜异位症中过表达。因此，抑制17 β HSD 1是治疗这些疾病的一种有前景的策略。在本论文中，我们研究了T47-D乳腺癌细胞的雌激素响应性细胞生长，非甾体17 β HSD 1抑制剂的细胞内抑制活性及其对雌激素依赖性细胞生长的影响。在相同浓度下，雌激素E1和E2诱导相同程度的生长刺激，表明E1快速细胞内转化为E2。抑制剂的应用选择性地防止刺激E1治疗引起的增殖，而E2介导的刺激不受影响。此外，从E1的细胞内E2形成被显著抑制，IC 50值在纳摩尔范围内。总之，我们的研究结果强烈支持非甾体17 β HSD 1抑制剂治疗雌激素依赖性疾病的适用性。(C)2009爱思唯尔有限公司保留所有权利。
The most potent estrogen estradiol (E2) plays a pivotal role in the initiation and progression of estrogen dependent diseases. 17 beta-Hydroxysteroid dehydrogenase type 1 (17 beta HSD1) catalyses the NADPH-dependent E2-formation from estrone (E1). It is often overexpressed in breast cancer and endometriosis. For this reason, inhibition of 17 beta HSD1 is a promising strategy for the treatment of these diseases. In the present paper, we investigate the estrogen responsive cell growth of T47-D breast cancer cells, the intracellular inhibitory activity of non-steroidal 17 beta HSD1-inhibitors and their effects on estrogen dependent cell growth in vitro. At equal concentrations the estrogens E1 and E2 induced the same extent of growth stimulation indicating fast intracellular conversion of E1 into E2. Application of inhibitors selectively prevented stimulation of proliferation evoked by E1-treatment whereas E2-mediated stimulation was not affected. Furthermore, intracellular E2-formation from E1 was significantly inhibited with IC50-values in the nanomolar range. In conclusion, our findings strongly support suitability of non-steroidal 17 beta HSD1-inhibitors for the treatment of estrogen dependent diseases. (C) 2009 Elsevier Ltd. All rights reserved.