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  2. BNIP3 as a potential target of esculetin for treating ovarian cancer and prognostic biomarker in ovarian cancer patients

BNIP3 as a potential target of esculetin for treating ovarian cancer and prognostic biomarker in ovarian cancer patients

  • Eur J Pharmacol. 2025 Jul 15:999:177698. doi: 10.1016/j.ejphar.2025.177698.
Wen Fan 1 Yongjun Zhang 1 Xiangqun Yang 1 Zhenyan Liu 1 Xingyan Wu 1 Lvzhou Li 2 Taoyu Zhao 2 Haoran Li 3 Xiaolin Liu 4 Daolei Cui 5 Qianqian Wan 6 Wenliang Li 1 Hongying Yang 7 Hongping Zhang 8 Yue Jia 9
Affiliations

Affiliations

  • 1 Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, 650118, China.
  • 2 Department of Obstetrics and Gynecology, Dehong Affiliated Hospital of Kunming Medical University, Dehong People's Hospital of Yunnan Province, Dehong, 678400, China.
  • 3 Medical School, Kunming University of Science and Technology, Kunming, 650500, China.
  • 4 Department of Gastroenterology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China.
  • 5 Institute of Environmental Remediation and Human Health, School of Ecology and Environment, Southwest Forestry University, Kunming, 650224, China.
  • 6 Medical Affairs Department, The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, 650021, China.
  • 7 Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, 650118, China. Electronic address: Yanghy913@126.com.
  • 8 Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, 650118, China. Electronic address: kmzhp@126.com.
  • 9 Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, 650118, China. Electronic address: kuailejy999@163.com.
Abstract

Among gynecological tumors, ovarian Cancer has the highest mortality rate and worst prognosis. Therefore, it is crucial to identify and develop novel methods and targets for treating ovarian Cancer. Previous studies have shown that esculetin exerts antitumor effects in a variety of cancers, however, its anti-ovarian Cancer effects and mechanisms of action remain unclear. In the present study, we investigated the anti-ovarian Cancer effects and mechanisms of esculetin in A2780 and OVCAR3 ovarian Cancer cells and established an xenograft ovarian Cancer mouse model. Esculetin significantly inhibited ovarian Cancer cell proliferation, blocked cell cycle progression, and promoted Apoptosis and DNA damage in a concentration-dependent manner. Furthermore, esculetin inhibited tumor growth in an xenograft ovarian Cancer mouse model. Moreover, RNA-seq showed that 2114 genes were significantly altered in A2780 cells after esculetin treatment. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that these differentially expressed genes were mainly enriched in the calcium, HIF-1, and Rap1 signaling pathways. Interestingly, BNIP3 expression was notably upregulated in ovarian Cancer cells after esculetin treatment. Finally, we found that low BNIP3 expression was correlated with poor prognosis in patients with ovarian Cancer. These results prove that esculetin may be a valuable anti-ovarian Cancer drug, and that BNIP3 is a potential treatment target for esculetin and a potential prognostic biomarker for ovarian Cancer.

Keywords

BNIP3; Cell apoptosis; Cell damage; Esculetin; Ovarian cancer.

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