Blockage of the STAT3 signaling pathway with a decoy oligonucleotide suppresses growth of human malignant glioma cells.
Gliomas are the most common type of primary tumor in the human central nervous system. STAT3, a signal transducer and activator of transcription 3, is over expressed in gliomas. Its involvement in tumorgenesis can be attributed to its ability to induce cell proliferation and inhibit apoptosis. Double-stranded decoy oligodeoxynucleotides (ODNs) which correspond closely to the STAT3 response element within the c-fos promoter are a potential tool for inhibiting a variety of tumor cell growth. To investigate its therapeutic potential in malignant gliomas, a 15-mer double-stranded decoy ODN mimicking STAT3-specific cis-elements was transfected into two glioma cell lines, U251 and A172. The STAT3 decoy ODN treatment specifically blocked STAT3 signaling and subsequently inhibited U251 and A172 cell proliferation by inducing apoptosis and cell-cycle arrest. The ODN treatment also decreased transcription and translation of downstream STAT3 target genes including c-myc, cyclin D1 and bcl-xl in both cell lines. Thus, targeted blockade of the STAT3 signaling pathway with a decoy ODN is a potential anti-glioma therapeutic approach.
Gu
Jinhai
J
Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, People's Republic of China.
Li
Gang
G
Sun
Tao
T
Su
Yuhang
Y
Zhang
Xulong
X
Shen
Jie
J
Tian
Zhigang
Z
Zhang
Jian
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018816:Genes, cdc / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006131:Growth Inhibitors / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D009841:Oligonucleotides / Q000235:genetics / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection; D051020:bcl-X Protein / Q000235:genetics
D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; D006131:Growth Inhibitors; C489427:MYC protein, human; D009841:Oligonucleotides; D016271:Proto-Oncogene Proteins c-myc; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051020:bcl-X Protein; D019938:Cyclin D1