title: Hypersensitivity to aurora kinase inhibitors in cells resistant against platinum- containing anticancer agents.
abstract: The aurora kinases are serine/threonine kinases that are essential for mitosis and contribute to tumorigenesis. Therefore, aurora kinases hold promise for molecularly targeted therapy. In the present study, we demonstrated that aurora B kinase (AURKB) is overexpressed in both cisplatin- and oxaliplatin-resistant cells. Downregulation of AURKB sensitized cells to both cisplatin and oxaliplatin, but not to paclitaxel, 5-FU or hydrogen peroxide. Interestingly, we found that both cisplatin- and oxaliplatin-resistant cells were hypersensitive to the AURKB specific inhibitors, AZD1152 HQPA and ZM447439, suggesting that both cisplatin- and oxaliplatinresistant cells develop an addiction to AURKB. These data provide evidence that aurora kinase inhibitors can overcome both cisplatin and oxaliplatin resistance. Therefore, AURKB inhibitors could offer potential benefits if used after first-line platinum-based chemotherapy.
authors: Masaki
authors: M
authors: Akiyama
authors: Hiroto
authors: H
authors: Izumi
authors: Ke-Yong
authors: KY
authors: Wang
authors: Takahiro
authors: T
authors: Yamaguchi
authors: Akihiro
authors: A
authors: Kuma
authors: Noriaki
authors: N
authors: Kitamura
authors: Yoshikazu
authors: Y
authors: Harada
authors: Ryoichi
authors: R
authors: Oya
authors: Koji
authors: K
authors: Yamaguchi
authors: Yoshiko
authors: Y
authors: Iwai
authors: President Laboratory, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan. k-kohno@med.uoeh-u.ac.jp.
authors: Kimitoshi
authors: K
authors: Kohno
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D064127:Aurora Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D010755:Organophosphates / Q000494:pharmacology; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology
chemical_list: C520647:2-((3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1H-pyrazol-3-yl)amino)quinazolin-7-yl)oxy)propyl)(ethyl)amino)ethyl dihydrogen phosphate; C474722:4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline; D000970:Antineoplastic Agents; D001549:Benzamides; D010755:Organophosphates; D009944:Organoplatinum Compounds; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077150:Oxaliplatin; D064127:Aurora Kinases; D002945:Cisplatin