孕激素对乳腺癌细胞中雌激素代谢酶的影响  

Effect of progestogen on estrogen metabolic enzyme in breast cancer cells

作　　者：马小平[1] 徐冰[1] 戴淑真[1] 姚勤[1] 

机构地区：[1]青岛大学医学院附属医院妇科,山东青岛266003

出　　处：《中国妇幼保健》2009年第16期2263-2266,共4页Maternal and Child Health Care of China

摘　　要：目的:选取5种常用于激素替代治疗(HRT)的孕激素,体外检测其不同类型、不同浓度、不同用药方式对乳腺癌细胞中雌激素代谢酶的影响。方法:培养人乳腺癌细胞T47D,MCF-7和MCF-7/aro,经E2和不同类型、不同浓度孕激素(P)作用后,Northern Blotting或RT-PCR技术检测雌激素代谢酶的mRNA表达,同位素标记的底物用于酶的活性测定。进一步模拟活体HRT,建立序贯治疗(SCR)和连续联合用药(CCR)的体外细胞模型。结果:与单用E2组相比,安宫黄体酮(MPA,10-8M-10-6M)与E2(10-8M)共同作用后,可上调雌激素活化酶芳香化酶、17β羟基甾醇脱氢酶Ⅰ型(17β-HSD1)、硫酸酯酶(STS)的活性并使mRNA表达升高。黄体酮(P4)也有上述作用,但是影响较小。左炔诺孕酮(LNG)、炔诺酮(NET)和地诺孕酮(DNG)对酶没有刺激作用。未见孕激素对雌激素抑制酶17β羟基甾醇脱氢酶Ⅱ型(17β-HSD2)和硫酸酯转移酶具有刺激作用。CCR体外细胞模型中检测到芳香化酶和17β-HSD1活性增加,而SCR模型中没有明显的酶刺激反应。结论:孕激素不同类型、不同用药方式对乳腺癌细胞中的雌激素代谢酶产生不同的作用,与其他孕激素相比,MPA对酶的刺激作用最强,其用于HRT是否通过上调酶的活性增加乳腺癌发病风险,尚有待研究。Objective： Five progestogens commonly used in hormone replacement therapy （HRT） were selected to investigate the effects on estrogen metabolic enzyme in human breast cancer cells by different types, concentrations and administration methods in vitro. Methods ： The human breast cancer cell lines T47D, MCF - 7 and MCF - 7/aro were treated by estradiol （ E2 ） and progestogens （P） and cultured for 24 - 72 hours. The expression levels of estrogen metabolic enzyme mRNA were determined by Northern Blotting or RT - PCR, and enzyme activities by radiolabeled substrates. To mimic the in vivo conditions of HRT, the in vitro models for continuous combined regimen （CCR） and sequential combined regimen （SCR） were established. Results： Medroxyprogesterone acetate （MPA, 10^-8 M - 10^-6 M） plus E2 （10^8 M） stimulated mRNA expression and enzymatic activity of estrogen metabolic enzyme aromatase, 17β -hydroxysteroid dehydrogenase type I （17β - HSD I ） and sulfatase compared with those of E2 only. Progesterone plus E2 also stimulated aromatase and sulfatase, but to a lower magnitude. Other progestogens including levonorgestrel, norethindrone and dienogest did not show significant stimu- lation on the three enzymes. Aromatase and 17β - HSD1 were stimulated in the CCR model in vitro, whereas no significant stimulation was observed in the SCR model. Conclusion ： Progestogens exert different actions on estrogen metabolic enzyme in breast cancer ceils by different types and administration methods in vitro. Compared to other progestogens, MPA presents the most significant stimulation on enzymes. Further studies are needed to elucidate whether MPA, which currently used in HRT, leads to a higher risk of breast cancer development than the other progestogens by up - regulation of estrogen metabolic enzyme.

关 键 词：激素替代治疗 人乳腺癌细胞 孕激素 雌激素代谢酶 

分 类 号：R73-3[医药卫生—肿瘤]