Paris saponin VII reverses resistance to PARP inhibitors by regulating ovarian cancer tumor angiogenesis and glycolysis through the RORα/ECM1/VEGFR2 signaling axis

Wang, Mengfei; Yuan, Chenyue; Wu, Zong; Xu, Meng; Chen, Ziqi; Yao, Jialiang; Que, Zujun; Tian, Jianhui; Leung, Elaine Lai-Han; Wang, Ziliang

doi:10.7150/ijbs.91861

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Theranostics

International Journal of Medical Sciences

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Int J Biol Sci 2024; 20(7):2454-2475. doi:10.7150/ijbs.91861 This issue Cite

Research Paper

Paris saponin VII reverses resistance to PARP inhibitors by regulating ovarian cancer tumor angiogenesis and glycolysis through the RORα/ECM1/VEGFR2 signaling axis

Mengfei Wang^1#, Chenyue Yuan^1#, Zong Wu^1#, Meng Xu¹, Ziqi Chen¹, Jialiang Yao², Zujun Que², Jianhui Tian^2✉, Elaine Lai-Han Leung^3✉, Ziliang Wang^1✉

1. 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.
#These authors contributed equally to this work.

✉ Corresponding authors: Ziliang Wang, Cancer Institute, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 274 Middle Zhijiang Road, Shanghai 200071, China. E-mail: wangziliangedu More

Citation:

Wang M, Yuan C, Wu Z, Xu M, Chen Z, Yao J, Que Z, Tian J, Leung ELH, Wang Z. Paris saponin VII reverses resistance to PARP inhibitors by regulating ovarian cancer tumor angiogenesis and glycolysis through the RORα/ECM1/VEGFR2 signaling axis. Int J Biol Sci 2024; 20(7):2454-2475. doi:10.7150/ijbs.91861. https://www.ijbs.com/v20p2454.htm

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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.

Keywords: Paris saponin VII, PARPi resistance, RORα, ECM1, VEGFR2, glycolysis, angiogenesis, ovarian cancer.

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APA

Wang, M., Yuan, C., Wu, Z., Xu, M., Chen, Z., Yao, J., Que, Z., Tian, J., Leung, E.L.H., Wang, Z. (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. https://doi.org/10.7150/ijbs.91861.

ACS

Wang, M.; Yuan, C.; Wu, Z.; Xu, M.; Chen, Z.; Yao, J.; Que, Z.; Tian, J.; Leung, E.L.H.; Wang, Z. Paris saponin VII reverses resistance to PARP inhibitors by regulating ovarian cancer tumor angiogenesis and glycolysis through the RORα/ECM1/VEGFR2 signaling axis. Int. J. Biol. Sci. 2024, 20 (7), 2454-2475. DOI: 10.7150/ijbs.91861.

NLM

CSE

Wang M, Yuan C, Wu Z, Xu M, Chen Z, Yao J, Que Z, Tian J, Leung ELH, Wang Z. 2024. Paris saponin VII reverses resistance to PARP inhibitors by regulating ovarian cancer tumor angiogenesis and glycolysis through the RORα/ECM1/VEGFR2 signaling axis. Int J Biol Sci. 20(7):2454-2475.

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