Novel Aurora A Kinase Inhibitor Fangchinoline Enhances Cisplatin–DNA Adducts and Cisplatin Therapeutic Efficacy in OVCAR-3 Ovarian Cancer Cells-Derived Xenograft Model

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题名:	Novel Aurora A Kinase Inhibitor Fangchinoline Enhances Cisplatin–DNA Adducts and Cisplatin Therapeutic Efficacy in OVCAR-3 Ovarian Cancer Cells-Derived Xenograft Model
作者:	Winar, Daniel;Winardi, Daniel;Chu, Pei-Yi;Chu, Pei-Yi;Chen, Guan-Yu;Chen, Guan-Yu;Wang, Ke;Wang, Ke;Hsu, Wei-Yu;Hsu, Wei-Yu;Ching-Liang;Hsieh, Ching-Liang;Yung-Hsiang;Chen, Yung-Hsiang;吳永昌;Wu, Yang-Chang;Juan-Cheng, Y;Yang, Juan-Cheng
贡献者:	醫學暨健康學院醫學檢驗暨生物技術學系
关键词:	Aurora A kinase;cisplatin;fangchinoline;inhibitor;mice;ovarian cancer.
日期:	2022-02-01
上传时间:	2023-03-29 02:23:29 (UTC+0)
出版者:	亞洲大學
摘要:	Aurora A kinase (Aurora A) is a serine/threonine kinase regulating control of multiple events during cell-cycle progression. Playing roles in promoting proliferation and inhibiting cell death in cancer cells leads Aurora A to become a target for cancer therapy. It is overexpressed and associated with a poor prognosis in ovarian cancer. Improving cisplatin therapy outcomes remains an important issue for advanced-stage ovarian cancer treatment, and Aurora A inhibitors may improve it. In the present study, we identified natural compounds with higher docking scores than the known Aurora A ligand through structure-based virtual screening, including the natural compound fangchinoline, which has been associated with anticancer activities but not yet investigated in ovarian cancer. The binding and inhibition of Aurora A by fangchinoline were verified using cellular thermal shift and enzyme activity assays. Fangchinoline reduced viability and proliferation in ovarian cancer cell lines. Combination fangchinoline and cisplatin treatment enhanced cisplatin-DNA adduct levels, and the combination index revealed synergistic effects on cell viability. An in vivo study showed that fangchinoline significantly enhanced cisplatin therapeutic effects in OVCAR-3 ovarian cancer-bearing mice. Fangchinoline may inhibit tumor growth and enhance cisplatin therapy in ovarian cancer. This study reveals a novel Aurora A inhibitor, fangchinoline, as a potentially viable adjuvant for ovarian cancer therapy.
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