title: Noscapine sensitizes chemoresistant ovarian cancer cells to cisplatin through inhibition of HIF-1α.
abstract: Hypoxia-inducible factor 1 alpha (HIF-1α) is closely related with chemoresistance of solid tumors. The purpose of this study was to investigate the ability of noscapine to inhibit HIF-1α and sensitize ovarian cancer cells to cisplatin (DDP) under hypoxic conditions. Herein, we report that noscapine sensitized cobalt-induced chemoresistant ovarian cancer cells to DDP-induced apoptosis and inhibition of cell proliferation. Noscapine also promoted proteasome-mediated degradation of cobalt-stabilized HIF-1α protein, with subsequent inhibition of HIF-1 transcriptional activity. These data establish noscapine as a small molecule inhibitor of HIF-1α and provide an evidence for its combination with DDP in combating ovarian cancer chemoresistance.
authors.affiliation: Institute of Pathology of Tongji Hospital, Department of Pathology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Su
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.forename: Qilin
authors.initials: Q
authors.lastname: Ao
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xun
authors.initials: X
authors.lastname: Tian
authors.forename: Yong
authors.initials: Y
authors.lastname: Fang
authors.forename: Yunping
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002469:Cell Separation; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors*; D009665:Noscapine / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009665:Noscapine; D002945:Cisplatin