Nguyen B L, Ferme I, Chetrite G, Pasqualini J R
C.N.R.S. Steroid Hormone Research Unit, Foundation for Hormone Research, Paris, France.
J Steroid Biochem Mol Biol. 1993 Jul;46(1):17-23. doi: 10.1016/0960-0760(93)90204-a.
In the present studies the action of Danazol on the conversion of estrone sulfate (E1S) to estradiol (E2) as well as on the sulfatase activity in the MCF-7 and T-47D, hormone-dependent, and MDA-MB-231, hormone-independent, mammary cancer cell lines was explored. Using intact cells we observed that Danazol blocks very significantly the radioactivity uptake and the conversion of [3H]E1S to E2 in all the cells studied. In particular, a very strong effect (85% decrease of these parameters versus the control values) is observed in the T-47D cells. In another series of studies using cell homogenates it is observed that Danazol inhibits the sulfatase activity in all these cell lines. The effect of Danazol is dose-dependent and significant from a concentration of 1 microM. At concentrations of 8 microM E1S, 10(-5) M Danazol, the inhibition of sulfatase activity is 38% in MCF-7, 36% in MDA-MB-231, and 27% in T-47D cells. Analysis by Lineweaver-Burk plot shows that the inhibitory effect is competitive. As E1S is one of the main sources of E2 in human mammary tumors, the present data could open new possibilities for therapeutic applications in hormone-dependent breast cancer.
在本研究中，探讨了达那唑对硫酸雌酮（E1S）转化为雌二醇（E2）的作用，以及对激素依赖性的MCF-7和T-47D乳腺癌细胞系和激素非依赖性的MDA-MB-231乳腺癌细胞系中硫酸酯酶活性的影响。使用完整细胞，我们观察到达那唑在所有研究的细胞中非常显著地阻断了放射性摄取以及[3H]E1S向E2的转化。特别是，在T-47D细胞中观察到非常强烈的作用（这些参数相对于对照值降低了85%）。在另一系列使用细胞匀浆的研究中，观察到达那唑抑制了所有这些细胞系中的硫酸酯酶活性。达那唑的作用呈剂量依赖性，从1 microM的浓度起就具有显著作用。在8 microM E1S、10(-5) M达那唑的浓度下，MCF-7细胞中硫酸酯酶活性的抑制率为38%，MDA-MB-231细胞中为36%，T-47D细胞中为27%。通过Lineweaver-Burk图分析表明，抑制作用是竞争性的。由于E1S是人类乳腺肿瘤中E2的主要来源之一，目前的数据可能为激素依赖性乳腺癌的治疗应用开辟新的可能性。
