Direct antiproliferative effect of nonsteroidal 17β-hydroxysteroid dehydrogenase type 1 inhibitors in vitro
Direct antiproliferative effect of nonsteroidal 17β-hydroxysteroid dehydrogenase type 1 inhibitors in vitro
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非甾体17β-羟基类固醇脱氢酶1型抑制剂的体外直接抗增殖作用
DOI：
10.3109/14756366.2012.672414
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发表时间：
2013
影响因子：
5.6
通讯作者：
I. Zupkó
中科院分区：
文献类型：
--
作者：
Á. Berényi;Martin Frotscher;S. Marchais;R. Hartmann;Renáta Minorics;I. Ocsovszki;G. Falkay;I. Zupkó
抑制雌激素的局部形成似乎是激素依赖性疾病药物干预的一个有吸引力的策略。研究了10种非甾体17β-羟基类固醇脱氢酶1型（17β-HSD1）抑制剂对人妇科肿瘤细胞系的直接抗增殖作用。通过细胞周期分析、荧光显微镜、BrdU测定、caspase-3活性测定和细胞周期调控因子mRNA水平的定量表达来初步探讨其抗增殖作用的机制。用某些化合物处理HeLa细胞导致G1-S转换的浓度依赖性抑制和凋亡群体的增加。最有效的药物增加肿瘤抑制因子p21和p53的表达，而下调CDK2和Rb的表达。这些化合物的抗癌作用与17β- hsd1的抑制能力无关。这些结果表明，将直接抗增殖活性和17β-HSD1抑制作用结合起来，产生具有双重作用模式的新型药物是可能的。
Inhibition of the local formation of estrogens seems to be an attractive strategy for pharmacological intervention in hormone-dependent disorders. The direct antiproliferative properties of ten nonsteroidal 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) inhibitors were investigated on human cancer cell lines of gynecological origin. The mechanism of the antiproliferative action was approximated by cell cycle analysis, fluorescent microscopy, BrdU assay, determination of caspase-3 activity and quantification of the expression of cell cycle regulators at mRNA level. Treatment of HeLa cells with some of the compounds resulted in a concentration-dependent inhibition of the G1–S transition and an increase in the apoptotic population. The most effective agents increased the expression of tumor suppressors p21 and p53, while CDK2 and Rb were down-regulated. The reported anticancer actions of the tested compounds are independent of the 17β-HSD1-inhibiting capacity. These results indicate that it is possible to combine direct antiproliferative activity and 17β-HSD1 inhibition resulting in novel agents with dual mode of action.
DOI：
10.1046/j.1432-1327.1998.2520169.x
发表时间：
1998-02-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Thompson, DA;Weigel, RJ
通讯作者：
Weigel, RJ