title: Targeted blockage of signal transducer and activator of transcription 5 signaling pathway with decoy oligodeoxynucleotides suppresses leukemic K562 cell growth.
abstract: 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.
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Department of Clinical Hematology, Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Wang
authors.forename: Jianming
authors.initials: J
authors.lastname: Zeng
authors.forename: Mei
authors.initials: M
authors.lastname: Shi
authors.forename: Shiqiao
authors.initials: S
authors.lastname: Zhao
authors.forename: Weijun
authors.initials: W
authors.lastname: Bai
authors.forename: Weixi
authors.initials: W
authors.lastname: Cao
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Tu
authors.forename: Zonggan
authors.initials: Z
authors.lastname: Huang
authors.forename: Wenli
authors.initials: W
authors.lastname: Feng
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000235:genetics / Q000473:pathology*; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013379:Substrate Specificity; D015533:Transcriptional Activation / Q000187:drug effects; D051020:bcl-X Protein / Q000235:genetics
chemical_list: C489427:MYC protein, human; D009838:Oligodeoxyribonucleotides; D016271:Proto-Oncogene Proteins c-myc; D050799:STAT5 Transcription Factor; D051020:bcl-X Protein; D019938:Cyclin D1