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Paris saponin VII reverses resistance to PARP inhibitors by regulating ovarian cancer tumor angiogenesis and glycolysis through the RORα/ECM1/VEGFR2 signaling axis.
Wang MengFei1; Yuan ChenYue1; Wu Zong1; Xu Meng1; Chen ZiQi1; Yao JiaLiang2; Que ZuJun2; Tian JianHui2; Leung Elaine Lai Han3; Wang ZiLiang1
2024-04
Source PublicationInternational Journal of Biological Sciences
ISSN1449-2288
Volume20Issue:7Pages:2454-2475
Abstract

The emergence of Poly (ADP-ribose) polymerase inhibitors (PARPi) has marked the beginning of a precise targeted therapy era for ovarian cancer. However, an increasing number of patients are experiencing primary or acquired resistance to PARPi, severely limiting its clinical application. Deciphering the underlying mechanisms of PARPi resistance and discovering new therapeutic targets is an urgent and critical issue to address. In this study, we observed a close correlation between glycolysis, tumor angiogenesis, and PARPi resistance in ovarian cancer. Furthermore, we discovered that the natural compound Paris saponin VII (PS VII) partially reversed PARPi resistance in ovarian cancer and demonstrated synergistic therapeutic effects when combined with PARPi. Additionally, we found that PS VII potentially hindered glycolysis and angiogenesis in PARPi-resistant ovarian cancer cells by binding and stabilizing the expression of RORα, thus further inhibiting ECM1 and interfering with the VEGFR2/FAK/AKT/GSK3β signaling pathway. Our research provides new targeted treatment for clinical ovarian cancer therapy and brings new hope to patients with PARPi-resistant ovarian cancer, effectively expanding the application of PARPi in clinical treatment.

KeywordAngiogenesis Ecm1 Glycolysis Ovarian Cancer Paris Saponin Vii Parpi Resistance Rorα Vegfr2
DOI10.7150/ijbs.91861
URLView the original
Indexed BySCIE
WOS Research AreaBiochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
WOS SubjectBiochemistry & Molecular Biology ; Biology
WOS IDWOS:001229795500005
PublisherIVYSPRING INT PUBL, PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
Scopus ID2-s2.0-85191695655
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Citation statistics
Document TypeJournal article
CollectionINSTITUTE OF COLLABORATIVE INNOVATION
DEPARTMENT OF BIOMEDICAL SCIENCES
Corresponding AuthorLeung Elaine Lai Han
Affiliation1.Cancer Institute, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
2.Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
3.Cancer Center, Faculty of Health Sciences; MOE Frontiers Science Center for Precision Oncology, University of Macau, Macau (SAR), China.
Corresponding Author AffilicationCancer Centre
Recommended Citation
GB/T 7714
Wang MengFei,Yuan ChenYue,Wu Zong,et al. Paris saponin VII reverses resistance to PARP inhibitors by regulating ovarian cancer tumor angiogenesis and glycolysis through the RORα/ECM1/VEGFR2 signaling axis.[J]. International Journal of Biological Sciences, 2024, 20(7), 2454-2475.
APA Wang MengFei., Yuan ChenYue., Wu Zong., Xu Meng., Chen ZiQi., Yao JiaLiang., Que ZuJun., Tian JianHui., Leung Elaine Lai Han., & Wang ZiLiang (2024). Paris saponin VII reverses resistance to PARP inhibitors by regulating ovarian cancer tumor angiogenesis and glycolysis through the RORα/ECM1/VEGFR2 signaling axis.. International Journal of Biological Sciences, 20(7), 2454-2475.
MLA Wang MengFei,et al."Paris saponin VII reverses resistance to PARP inhibitors by regulating ovarian cancer tumor angiogenesis and glycolysis through the RORα/ECM1/VEGFR2 signaling axis.".International Journal of Biological Sciences 20.7(2024):2454-2475.
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