title: In vitroevaluation of a combination treatment involving anticancer agents and an aurora kinase B inhibitor.
abstract: Aurora kinase B (AURKB) inhibitors are regarded as potential molecular-targeting drugs for cancer therapy. The present study evaluated the cytotoxic effect of a combination of AZD1152-hQPA, an AURKB inhibitor, and various anticancer agents on the HeLa human cervical cancer cell line, as well as its cisplatin-resistant equivalent HCP4 cell line. It was demonstrated that AZD1152-hQPA had an antagonistic effect on the cytotoxicity of cisplatin, etoposide and doxorubicin, but had a synergistic effect on that of all-trans-retinoic acid (ATRA), Am80 and TAC-101, when tested on HeLa cells. Cisplatin, etoposide and doxorubicin were shown to increase the cellular expression of AURKB, while ATRA, Am80 and TAC-101 downregulated its expression. These results suggested that AURKB expression is regulated by these anticancer agents at the transcriptional level, and that the level of expression of AURKB may influence the cytotoxic effect of AZD1152-hQPA. Therefore, when using anticancer agents, decreasing the expression of AURKB using a molecular-targeting drug may be an optimal therapeutic strategy.
authors.affiliation: Department of Occupational Pneumology, Institute of Industrial Ecological Science, University of Occupational and Environmental Health School of Medicine, Kitakyushu 807-8555, Japan; Department of Bioscience and Bioinformatics, Biomedical Informatics R&D Center, Kyushu Institute of Technology, Iizuka, Fukuoka 820-8502, Japan.
authors.forename: Senna
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Department of Occupational Pneumology, Institute of Industrial Ecological Science, University of Occupational and Environmental Health School of Medicine, Kitakyushu 807-8555, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Izumi
authors.affiliation: Department of Occupational Pneumology, Institute of Industrial Ecological Science, University of Occupational and Environmental Health School of Medicine, Kitakyushu 807-8555, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yoshiura
authors.affiliation: Department of Gastroenterological and General Surgery, Wakamatsu Hospital, University of Occupational and Environmental Health School of Medicine, Kitakyushu 808-0024, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nakayama
authors.affiliation: Department of Hematology, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Dentistry and Oral Surgery, University Hospital, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Harada
authors.affiliation: Department of Obstetrics and Gynecology, University of Occupational and Environmental Health School of Medicine, Kitakyushu 807-8555, Japan.
authors.forename: Chiho
authors.initials: C
authors.lastname: Koi
authors.affiliation: Department of Bioscience and Bioinformatics, Biomedical Informatics R&D Center, Kyushu Institute of Technology, Iizuka, Fukuoka 820-8502, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kurata
authors.affiliation: Department of Occupational Pneumology, Institute of Industrial Ecological Science, University of Occupational and Environmental Health School of Medicine, Kitakyushu 807-8555, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morimoto
keywords: anticancer agent; aurora kinase B; aurora kinase B inhibitor; combination index; combination treatment