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首页> 外文期刊>Life sciences >The effect of endogenous estradiol metabolites on the proliferation of human breast cancer cells.
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The effect of endogenous estradiol metabolites on the proliferation of human breast cancer cells.

机译：内源性雌二醇代谢产物对人乳腺癌细胞增殖的影响。

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摘要

Evidence is accumulating that estradiol metabolites may be involved in carcinogenesis as some metabolites exert proliferative and others anti-proliferative properties on human cancer cells. The present study is the first to investigate the effect of 14 endogenous estradiol metabolites on the proliferation of the human breast cancer cell line, MCF-7, in comparison with the effect of the parent substance 17beta-estradiol with special concern on high pharmacological concentrations. The steroids were tested in the range from 10(-8) to 10(-5) M on MCF-7 cells which were incubated for nine days. Estradiol and almost all A-ring metabolites displayed biphasic reactions on cell proliferation, i.e. stimulatory at low concentrations and inhibitory at the highest concentration, 10(-5) M. The D-ring metabolites did not show such clear biphasic patterns, in most of them the stimulatory effect prevailed at the highest dosage used. The strongest inhibitory effect was seen for the A-ring metabolite 2-methoxyestradiol at the concentrations of 10(-6) and 10(-5) M and the strongest stimulatory effect was noted for the D-ring metabolite estriol at the same concentrations.The results indicate that some A-ring metabolites might be suitable for breast cancer treatment when used in high dosages. This is of special interest, since many of these metabolites have very weak estrogenic activity.
机译：越来越多的证据表明，雌二醇代谢物可能与癌变有关，因为某些代谢物对人类癌细胞具有增生作用，而另一些则具有抗增生作用。本研究是第一个研究14种内源性雌二醇代谢产物对人乳腺癌细胞MCF-7增殖的影响，而母体物质17β-雌二醇对高药理学浓度的影响则与之比较。在孵育9天的MCF-7细胞上测试了类固醇在10（-8）至10（-5）M的范围内。雌二醇和几乎所有A环代谢物在细胞增殖上均表现出双相反应，即在低浓度时具有刺激作用，在最高浓度10（-5）M时具有抑制作用。在大多数情况下，D环代谢物未显示出如此清晰的双相模式。它们的刺激作用在最高剂量时占主导。在浓度为10（-6）和10（-5）M的情况下，对A环代谢物2-甲氧基雌二醇的抑制作用最强，而在相同浓度下，对D环代谢物雌三醇的刺激作用最强。结果表明，以高剂量使用时，某些A环代谢物可能适合乳腺癌的治疗。这是特别令人感兴趣的，因为许多这些代谢物的雌激素活性非常弱。

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