Cargando…

The Anti-Tumor Efficacy of Verbascoside on Ovarian Cancer via Facilitating CCN1-AKT/NF-κB Pathway-Mediated M1 Macrophage Polarization

BACKGROUND: Ovarian cancer (OC) is the leading cause of gynecological cancer-related mortality. Verbascoside (VB) is a phenylpropanoid glycoside from Chinese herbs, with anti-tumour activities. This study aimed to investigate the effects and mechanism of VB on OC. METHODS: OC cell lines SKOV3 and A2...

Descripción completa

Detalles Bibliográficos
Autores principales: Ren, Yu, He, Jinying, Zhao, Wenhua, Ma, Yuzhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249354/
https://www.ncbi.nlm.nih.gov/pubmed/35785168
http://dx.doi.org/10.3389/fonc.2022.901922
_version_ 1784739562283597824
author Ren, Yu
He, Jinying
Zhao, Wenhua
Ma, Yuzhen
author_facet Ren, Yu
He, Jinying
Zhao, Wenhua
Ma, Yuzhen
author_sort Ren, Yu
collection PubMed
description BACKGROUND: Ovarian cancer (OC) is the leading cause of gynecological cancer-related mortality. Verbascoside (VB) is a phenylpropanoid glycoside from Chinese herbs, with anti-tumour activities. This study aimed to investigate the effects and mechanism of VB on OC. METHODS: OC cell lines SKOV3 and A2780 were used in this study. Cell viability, proliferation, and migration were measured using CCK-8, clonogenic, and transwell assays, respectively. Apoptosis and M1/M2 macrophages were detected using flow cytometry. The interaction between VB and CCN1 was predicted by molecular docking. The mRNA expression of CCN1 was detected by RT-qPCR. The protein levels of CCN1, AKT, p-AKT, p65, and p-p65 were determined by western blotting. A xenograft mice model was established for in vivo validation. RESULTS: VB inhibited OC cell proliferation and migration in a dose-dependent manner, and promoted apoptosis and M1 macrophage polarization. VB downregulated CCN1 and inhibited the AKT/NF-κB pathway. LY294002, an AKT inhibitor, potentiated the anti-tumour effects of VB. CCN1 overexpression weakened the anti-tumour effects of VB and VB + LY294002. In vivo experiments verified that VB inhibited tumour growth and promoted M1 polarization, which is regulated by the CCN1-mediated AKT/NF-κB pathway. CONCLUSION: VB triggers the CCN1-AKT/NF-κB pathway-mediated M1 macrophage polarization for protecting against OC.
format Online
Article
Text
id pubmed-9249354
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-92493542022-07-02 The Anti-Tumor Efficacy of Verbascoside on Ovarian Cancer via Facilitating CCN1-AKT/NF-κB Pathway-Mediated M1 Macrophage Polarization Ren, Yu He, Jinying Zhao, Wenhua Ma, Yuzhen Front Oncol Oncology BACKGROUND: Ovarian cancer (OC) is the leading cause of gynecological cancer-related mortality. Verbascoside (VB) is a phenylpropanoid glycoside from Chinese herbs, with anti-tumour activities. This study aimed to investigate the effects and mechanism of VB on OC. METHODS: OC cell lines SKOV3 and A2780 were used in this study. Cell viability, proliferation, and migration were measured using CCK-8, clonogenic, and transwell assays, respectively. Apoptosis and M1/M2 macrophages were detected using flow cytometry. The interaction between VB and CCN1 was predicted by molecular docking. The mRNA expression of CCN1 was detected by RT-qPCR. The protein levels of CCN1, AKT, p-AKT, p65, and p-p65 were determined by western blotting. A xenograft mice model was established for in vivo validation. RESULTS: VB inhibited OC cell proliferation and migration in a dose-dependent manner, and promoted apoptosis and M1 macrophage polarization. VB downregulated CCN1 and inhibited the AKT/NF-κB pathway. LY294002, an AKT inhibitor, potentiated the anti-tumour effects of VB. CCN1 overexpression weakened the anti-tumour effects of VB and VB + LY294002. In vivo experiments verified that VB inhibited tumour growth and promoted M1 polarization, which is regulated by the CCN1-mediated AKT/NF-κB pathway. CONCLUSION: VB triggers the CCN1-AKT/NF-κB pathway-mediated M1 macrophage polarization for protecting against OC. Frontiers Media S.A. 2022-06-17 /pmc/articles/PMC9249354/ /pubmed/35785168 http://dx.doi.org/10.3389/fonc.2022.901922 Text en Copyright © 2022 Ren, He, Zhao and Ma https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Ren, Yu
He, Jinying
Zhao, Wenhua
Ma, Yuzhen
The Anti-Tumor Efficacy of Verbascoside on Ovarian Cancer via Facilitating CCN1-AKT/NF-κB Pathway-Mediated M1 Macrophage Polarization
title The Anti-Tumor Efficacy of Verbascoside on Ovarian Cancer via Facilitating CCN1-AKT/NF-κB Pathway-Mediated M1 Macrophage Polarization
title_full The Anti-Tumor Efficacy of Verbascoside on Ovarian Cancer via Facilitating CCN1-AKT/NF-κB Pathway-Mediated M1 Macrophage Polarization
title_fullStr The Anti-Tumor Efficacy of Verbascoside on Ovarian Cancer via Facilitating CCN1-AKT/NF-κB Pathway-Mediated M1 Macrophage Polarization
title_full_unstemmed The Anti-Tumor Efficacy of Verbascoside on Ovarian Cancer via Facilitating CCN1-AKT/NF-κB Pathway-Mediated M1 Macrophage Polarization
title_short The Anti-Tumor Efficacy of Verbascoside on Ovarian Cancer via Facilitating CCN1-AKT/NF-κB Pathway-Mediated M1 Macrophage Polarization
title_sort anti-tumor efficacy of verbascoside on ovarian cancer via facilitating ccn1-akt/nf-κb pathway-mediated m1 macrophage polarization
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249354/
https://www.ncbi.nlm.nih.gov/pubmed/35785168
http://dx.doi.org/10.3389/fonc.2022.901922
work_keys_str_mv AT renyu theantitumorefficacyofverbascosideonovariancancerviafacilitatingccn1aktnfkbpathwaymediatedm1macrophagepolarization
AT hejinying theantitumorefficacyofverbascosideonovariancancerviafacilitatingccn1aktnfkbpathwaymediatedm1macrophagepolarization
AT zhaowenhua theantitumorefficacyofverbascosideonovariancancerviafacilitatingccn1aktnfkbpathwaymediatedm1macrophagepolarization
AT mayuzhen theantitumorefficacyofverbascosideonovariancancerviafacilitatingccn1aktnfkbpathwaymediatedm1macrophagepolarization
AT renyu antitumorefficacyofverbascosideonovariancancerviafacilitatingccn1aktnfkbpathwaymediatedm1macrophagepolarization
AT hejinying antitumorefficacyofverbascosideonovariancancerviafacilitatingccn1aktnfkbpathwaymediatedm1macrophagepolarization
AT zhaowenhua antitumorefficacyofverbascosideonovariancancerviafacilitatingccn1aktnfkbpathwaymediatedm1macrophagepolarization
AT mayuzhen antitumorefficacyofverbascosideonovariancancerviafacilitatingccn1aktnfkbpathwaymediatedm1macrophagepolarization