Sakai Senna, Izumi Hiroto, Yoshiura Yukiko, Nakayama Yoshifumi, Yamaguchi Takahiro, Harada Yoshikazu, Koi Chiho, Kurata Hiroyuki, Morimoto Yasuo
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.
Department of Occupational Pneumology, Institute of Industrial Ecological Science, University of Occupational and Environmental Health School of Medicine, Kitakyushu 807-8555, Japan.
Oncol Lett. 2016 Nov;12(5):4263-4269. doi: 10.3892/ol.2016.5156. Epub 2016 Sep 20.
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.
极光激酶B（AURKB）抑制剂被视为癌症治疗的潜在分子靶向药物。本研究评估了AURKB抑制剂AZD1152-hQPA与多种抗癌药物联合使用对HeLa人宫颈癌细胞系及其顺铂耐药等效细胞系HCP4细胞系的细胞毒性作用。结果表明，在HeLa细胞上进行测试时，AZD1152-hQPA对顺铂、依托泊苷和阿霉素的细胞毒性具有拮抗作用，但对全反式维甲酸（ATRA）、Am80和TAC-101的细胞毒性具有协同作用。顺铂、依托泊苷和阿霉素可增加AURKB的细胞表达，而ATRA、Am80和TAC-101则下调其表达。这些结果表明，AURKB的表达在转录水平上受这些抗癌药物的调控，并且AURKB的表达水平可能影响AZD1152-hQPA的细胞毒性作用。因此，在使用抗癌药物时，使用分子靶向药物降低AURKB的表达可能是一种最佳治疗策略。
