STAT3-decoy oligodeoxynucleotide inhibits the growth of human lung cancer via down-regulating its target genes.
Double-stranded decoy oligodeoxynucleotide (ODN) is a promising approach for inhibiting gene transcription. Signal transducer and activator of transcription (STAT) 3, a potent transcription factor, is usually constitutively activated in a variety of malignancies, and considered as an attractive drug target. In this study, it was noted that STAT3 was overactivated in human lung cancer cells, and STAT3-decoy ODN, which was high-efficiently transfected into nucleus of cancer cells, significantly inhibited the proliferation of PG cells by inducing apoptosis or cell cycle arrest. The transcription levels of mcl-1, cyclin D1, bcl-xl and survivin were significantly decreased by 64.4, 56.1, 72.8% (P<0.01) and 31.8% (P<0.05), respectively; and the synthesis levels of bcl-xl and cyclin D1 in PG cells showed 64.5% (P<0.01) and 28.6% (P<0.05) decrease, respectively. Our study demonstrated that decoy-ODN targeting at activated STAT3 may potentially be used as an anti-lung cancer therapeutic approach.
Zhang
Xulong
X
Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, PR China.
Zhang
Jian
J
Wei
Haiming
H
Tian
Zhigang
Z
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000235:genetics; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008175:Lung Neoplasms / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D014162:Transfection; D051020:bcl-X Protein / Q000037:antagonists & inhibitors / Q000235:genetics
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; D000077022:Survivin; D051020:bcl-X Protein; D019938:Cyclin D1