刘延凤,许丽,金艺,索昊,李佳阳,徐海燕
LIU Yan-feng,XU Li,JIN Yi,SUO Hao,LI Jia-yang,XU Hai-yan

• 1:沈阳药科大学药学院

摘要(Abstract)：

目的研究硫酸雌酮对染料木素及其Ⅱ相结合物在乳腺细胞中代谢的影响。方法以人乳腺癌细胞系T47D和非癌乳腺细胞系MCF-10A为研究对象,采用体外孵化模型,将硫酸雌酮(estrone-3-sulfate,E1S)分别与染料木素(genistein,GEN)及染料木素-4'-硫酸结合物(genistein-4'-sulfate,G-4'-S)、染料木素-7-硫酸结合物(genistein-7-sulfate,G-7-S)、染料木素-4'-葡萄糖醛酸结合物(genistein-4'-glucuronide,G-4'-G)和染料木素-7-葡萄糖醛酸结合物(genistein-7-glucuronide,G-7-G)4个染料木素Ⅱ相结合物共同孵化24 h后,收集孵化液,采用LC-MS/MS法定量测定孵化液中相应代谢产物的浓度。结果在T47D和MCF-10A细胞中,E1S可明显抑制GEN转化为G-7-S和G-4'-S;E1S还可明显抑制G-7-G的生物转化。此外,E1S可促进MCF-10A细胞中G-4'-S转化为G-7-S。E1S对T47D和MCF-10A细胞中G-4'-G和G-7-S的代谢无显著性影响。结论 E1S影响GEN、G-7-G和G-4'-S在乳腺细胞中的代谢,对G-4'-G和G-7-S的代谢无明显作用。
Objective To investigate the effect of estrone sulfate on the metabolism of genistein and its phase II conjugates in human breast cell lines. Methods Genistein and its phase II conjugates( genistein-4'-sulfate,genistein-7-sulfate,genistein-4'-glucuronide,genistein-7-glucuronide) w ere incubated w ith or w ithout estrone sulfate in T47D cells and MCF-10A cells,respectively. Incubation fluid w as collected and the amounts of the formed metabolites of the substances w ere quantitatively determined by liquid chromatography coupled w ith tandem mass spectrometer. Results Estrone sulfate obviously inhibited the bio-transformation of GEN to G-7-S and G-4'-S in T47D and MCF-10A cells. Estrone sulfate also decreased the metabolism of G-7-G in both cells. Estrone sulfate clearly stimulated the formation of G-7-S from G-4'-S in MCF-10A cells. How ever,estrone sulfate had no effect on the metabolism of G-4'-G and G-7-S in these cells. Conclusions This is the first time to investigate the effect of estrone sulfate on the metabolism of genistein and its phase II conjugates in human breast cells. Estrone sulfate obviously affects the metabolism of GEN,G-7-G and G-4'-S in human breast cell lines,but it doesn't influence the metabolism of G-4'-G and G-7-S.

关键词(KeyWords)： 染料木素;Ⅱ相结合物;硫酸雌酮;药物代谢;人乳腺细胞
genistein;phase II conjugates;estrone sulfate;drug metabolism;human breast cell lines

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金资助项目(30801420)

作者(Author): 刘延凤,许丽,金艺,索昊,李佳阳,徐海燕
LIU Yan-feng,XU Li,JIN Yi,SUO Hao,LI Jia-yang,XU Hai-yan

DOI: 10.14066/j.cnki.cn21-1349/r.2013.11.013

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