Auvray P, Sourdaine P, Séralini G E
Lab. Biochimie et Biologie Moléculaire, IBBA, Université de Caen, France.
Biochem Biophys Res Commun. 1998 Dec 9;253(1):1-9. doi: 10.1006/bbrc.1998.9683.
Estrogen-dependent diseases, especially breast cancers, are frequently treated with aromatase inhibitors. Another more recent strategy is the antisense technology. In this study, after predicting aromatase mRNA secondary structure, we describe the design, the efficiency, and the toxicity of two antisense phosphorothioate oligodeoxynucleotides (PAAn-1b and PAAn-E) directed toward aromatase mRNA. Indeed, 2 microM PAAn-1b and PAAn-E encapsulated with 54 microM polyethylenimine inhibit aromatase activity by 71 and 79%, respectively, in transfected 293 cells, with IC50 values of 0.2 and 0.6 microM. The mechanism of inhibition appears to be specific after using sense and scramble oligodeoxynucleotides as controls and largely decreases aromatase mRNA and protein amounts. Moreover, PAAn-1b and PAAn-E are not cytotoxic for 293 cells. This study finally provides a new strategy for aromatase inhibition. It offers new tools for studying aromatase gene expression and its role in cancer for instance, and this could be of help for the therapy of estrogen-dependent diseases.
雌激素依赖性疾病，尤其是乳腺癌，常用芳香化酶抑制剂进行治疗。另一种更新的策略是反义技术。在本研究中，预测芳香化酶mRNA二级结构后，我们描述了两种针对芳香化酶mRNA的反义硫代磷酸寡脱氧核苷酸（PAAn - 1b和PAAn - E）的设计、效率及毒性。实际上，用54 μM聚乙烯亚胺包裹的2 μM PAAn - 1b和PAAn - E分别使转染的293细胞中的芳香化酶活性抑制71%和79%，IC50值分别为0.2 μM和0.6 μM。以正义和随机寡脱氧核苷酸作为对照后，抑制机制似乎具有特异性，且大幅降低了芳香化酶mRNA和蛋白量。此外，PAAn - 1b和PAAn - E对293细胞无细胞毒性。本研究最终为芳香化酶抑制提供了一种新策略。例如，它为研究芳香化酶基因表达及其在癌症中的作用提供了新工具，这可能有助于雌激素依赖性疾病的治疗。
