title: HIF-1α decoy oligodeoxynucleotides inhibit HIF-1α signaling and breast cancer proliferation.
abstract: Although HIF-1α is considered an attractive target for the development of cancer therapies, like other transcriptional factors, it has been regarded as 'undruggable'. The decoy approach is a new class of antigene strategy that can be used to modulate the function of endogenous transcriptional factors. Here, we designed a decoy oligodeoxynucleotide (ODN) and tested its effect on the function of HIF-1α. We found the HIF-1α decoy ODN could efficiently enter into cells. Furthermore, these decoy ODNs can significantly block the expression of VEGFA, a known targeted gene of HIF-1α suggesting that the HIF-1α decoy ODNs can inhibit the function of HIF-1α. More importantly, the HIF-1α decoy ODN induced apoptosis and cell cycle arrest in MDA-MB-231 breast cancer cells. In summary, HIF-1α decoy ODNs can inhibit the function of HIF-1α and induce cancer cell apoptosis. Therefore, HIF-1α decoy ODNs should be further modified to improve their biological activity in vivo.
authors.affiliation: Outpatient Department, Gansu Provincial Hospital, Lanzhou 730000, P.R. China.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Plastic Surgery, General Hospital of Guangzhou Military Command, Guangzhou 510010, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Plastic Surgery, General Hospital of Guangzhou Military Command, Guangzhou 510010, P.R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Urology, General Hospital of Guangzhou Military Command, Guangzhou 510010, P.R. China.
authors.forename: Bote
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, General Hospital of Guangzhou Military Command, Guangzhou 510010, P.R. China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Zou
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009838:Oligodeoxyribonucleotides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A