Abstract
Paris polyphylla saponin II (PPII) has good biological activity in inhibiting tumor angiogenesis. However, the mechanism of its action is still unclear. This study first observed the inhibitory effect of PPII on cervical cancer cells (Hela) through the establishment of MTT and nude mouse subcutaneous transplantation tumor models. Afterwards, then, we collected Hela cell supernatant for culturing HUVEC cells and treated it with PPII. Observe the invasion, migration, and lumen formation ability of drugs through Transwell, cell scratch test, and angiogenesis experiment. MDC staining was used to observe positive staining in the perinuclear area, AO staining was used to observe acidic areas, and transmission electron microscopy staining was used to observe ultrastructure and autophagy. In addition, the effects of PPII on autophagy- and angiogenesis-related protein expression were detected by Western blotting and quantitative reverse transcriptase polymerase chain reaction. Finally, HUVECs were treated with autophagy inhibitors 3-MA, CQ, and PI3K inhibitor LY294002, respectively. The results showed that the autophagy level of cells treated with PPII was significantly increased. In addition, adding autophagy inhibitors can effectively inhibit angiogenesis in cervical cancer. Further research suggests that PPII induces autophagy in HUVEC cells by regulating the PI3K/AKT/mTOR signaling pathway, thereby affecting angiogenesis and inhibiting Hela cell proliferation, lumen formation, invasion, and migration.
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Funding
The present study was supported by the Fund of the National Nature Science Foundations grant nos. 81903859, 82305023, 81673650, and 81973488; Anhui Provincial Natural Science Foundation (2308085MH305); Key projects of natural science research in Anhui Universities (KJ2021A0591, 2022AH050529); the Innovation training program for college students in Anhui Province (S202110369078); the Key Natural Science Project of Anhui University of Chinese Medicine (grant number 2021zrzd08 to MengWang); and the first batch of talent support plan projects of Anhui University of Chinese medicine in 2022 (grant number 2022rcyb016).
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Q designed the study. H and J performed the experiments. J and J collected the data. M analyzed and interpreted the data. All the authors read and approve the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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SPF-grade BALB/c mice (5–6 weeks old, weighing 18–22 g) were purchased from Zhejiang Weitong Lihua Experimental Animal Technology Co., Ltd. All animal surgeries have been approved by the ethics committee, Anhui University of Traditional Chinese Medicine Experimental Animal Ethics Committee (AHUCM-mouse-2021100).
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Cheng, H., Long, J., Su, J. et al. Mechanism of Paris polyphylla saponin II inducing autophagic to inhibit angiogenesis of cervical cancer. Naunyn-Schmiedeberg's Arch Pharmacol 397, 3179–3194 (2024). https://doi.org/10.1007/s00210-023-02794-x
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DOI: https://doi.org/10.1007/s00210-023-02794-x