Mechanism of Paris polyphylla saponin II inducing autophagic to inhibit angiogenesis of cervical cancer.

Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0326264 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1912 (Electronic) Linking ISSN: 00281298 NLM ISO Abbreviation: Naunyn Schmiedebergs Arch Pharmacol Subsets: MEDLINE

Original Publication: Berlin, New York, Springer Verlag.

Uterine Cervical Neoplasms*/drug therapy ; Uterine Cervical Neoplasms*/pathology ; Uterine Cervical Neoplasms*/metabolism ; Saponins*/pharmacology ; Autophagy*/drug effects ; Neovascularization, Pathologic*/drug therapy ; Human Umbilical Vein Endothelial Cells*/drug effects ; Human Umbilical Vein Endothelial Cells*/metabolism ; Mice, Nude*; Humans ; HeLa Cells ; Female ; Animals ; TOR Serine-Threonine Kinases/metabolism ; Cell Movement/drug effects ; Angiogenesis Inhibitors/pharmacology ; Mice, Inbred BALB C ; Proto-Oncogene Proteins c-akt/metabolism ; Diosgenin/pharmacology ; Diosgenin/analogs & derivatives ; Diosgenin/therapeutic use ; Signal Transduction/drug effects ; Melanthiaceae/chemistry ; Xenograft Model Antitumor Assays ; Mice ; Antineoplastic Agents, Phytogenic/pharmacology ; Angiogenesis

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.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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2021zrzd08 The Key Natural Science Project of Anhui University of Chinese Medicine; 2308085MH305 Anhui Provincial Natural Science Foundation; KJ2021A0591，2022AH050529 Key projects of natural science research in Anhui Universities; 81903859, 82305023, 81673650, 81973488, The present study was supported by the Fund of the National Nature Science Foundations grant; S202110369078 he Innovation training program for college students in Anhui Province; 2022rcyb016 The first batch of talent support plan projects of Anhui University of Chinese medicine in 2022

Keywords: Paris polyphylla saponin II; Angiogenesis; Autophagy; Cervical cancer

0 (Saponins)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
0 (Angiogenesis Inhibitors)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
K49P2K8WLX (Diosgenin)
0 (ruscogenin-1-O-(glucopyranosyl-(1-2))(xylopyranosyl-(1-3))fucopyranoside)
0 (Antineoplastic Agents, Phytogenic)

Date Created: 20231031 Date Completed: 20240506 Latest Revision: 20240514

20240515

10.1007/s00210-023-02794-x

37906274