Key Laboratory of Laboratory Medical Diagnostics, Department of Clinical Hematology, Ministry of Education, Chongqing Medical University, Chongqing, China.
DNA Cell Biol. 2011 Feb;30(2):71-8. doi: 10.1089/dna.2010.1112. Epub 2010 Nov 22.
The protein signal transducer and activator of transcription 5 (STAT5) of the JAK/STAT pathway is constitutively activated because of its phosphorylation by tyrosine kinase activity of fusion protein BCR-ABL in chronic myelogenous leukemia (CML) cells. This study investigated the potential therapeutic effect of STAT5 decoy oligodeoxynucleotides (ODN) using leukemia K562 cells as a model. Our results showed that transfection of 21-mer-long STAT5 decoy ODN into K562 cells effectively inhibited cell proliferation and induced cell apoptosis. Further, STAT5 decoy ODN downregulated STAT5 targets bcl-xL, cyclinD1, and c-myc at both mRNA and protein levels in a sequence-specific manner. Collectively, these data demonstrate the therapeutic effect of blocking the STAT5 signal pathway by cis-element decoy for cancer characterized by constitutive STAT5 activation. Thus, our study provides support for STAT5 as a potential target downstream of BCR-ABL for CML treatment and helps establish the concept of targeting STAT5 by decoy ODN as a novel therapy approach for imatinib-resistant CML.
蛋白信号转导子和转录激活子 5（STAT5）的 JAK/STAT 通路由于其在慢性髓性白血病（CML）细胞中融合蛋白 BCR-ABL 的酪氨酸激酶活性的磷酸化而被持续激活。本研究使用白血病 K562 细胞作为模型，探讨了 STAT5 诱饵寡脱氧核苷酸（ODN）的潜在治疗效果。我们的结果表明，将 21 个碱基长的 STAT5 诱饵 ODN 转染到 K562 细胞中，可有效抑制细胞增殖并诱导细胞凋亡。此外，STAT5 诱饵 ODN 以序列特异性方式在 mRNA 和蛋白质水平下调 STAT5 靶标 bcl-xL、cyclinD1 和 c-myc。总之，这些数据表明，通过顺式元件诱饵阻断 STAT5 信号通路对具有持续 STAT5 激活特征的癌症具有治疗作用。因此，我们的研究为 STAT5 作为 CML 治疗中 BCR-ABL 的潜在下游靶点提供了支持，并有助于确立通过诱饵 ODN 靶向 STAT5 作为治疗伊马替尼耐药 CML 的新疗法的概念。
