Cargando…

Flavokawain B Weakens Gastric Cancer Progression via the TGF-β1/SMAD4 Pathway and Attenuates M2 Macrophage Polarization

This study was designed to observe the treatment effects of flavokawain B (FKB) on gastric cancer both in SGC-7901 cells and nude mice. When SGC-7901 cells were exposed to 10 μg/mL FKB, cellular proliferative and apoptotic capacities and cell cycle were detected utilizing CCK-8 and flow cytometry as...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhu, Yongzhao, Fan, Weining, Wang, Yuanzhen, Ding, Huan, Yang, Shaoqi, He, Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308533/
https://www.ncbi.nlm.nih.gov/pubmed/35879950
http://dx.doi.org/10.1155/2022/4903333
_version_ 1784753001905258496
author Zhu, Yongzhao
Fan, Weining
Wang, Yuanzhen
Ding, Huan
Yang, Shaoqi
He, Fang
author_facet Zhu, Yongzhao
Fan, Weining
Wang, Yuanzhen
Ding, Huan
Yang, Shaoqi
He, Fang
author_sort Zhu, Yongzhao
collection PubMed
description This study was designed to observe the treatment effects of flavokawain B (FKB) on gastric cancer both in SGC-7901 cells and nude mice. When SGC-7901 cells were exposed to 10 μg/mL FKB, cellular proliferative and apoptotic capacities and cell cycle were detected utilizing CCK-8 and flow cytometry assays. The results showed that FKB treatment induced cell apoptosis and G2/M arrest and suppressed cell proliferation for SGC-7901 cells. Western blot results showed that FKB upregulated proapoptotic proteins as well as downregulated antiapoptotic and cell cycle-related proteins in SGC-7901 cells. SMAD4, TGF-β1, and TSPAN12 proteins were tested in FKB-induced SGC-7901 cells. Following exposure to FKB, SMAD4, TGF-β1, and TSPAN12 expression was augmented in SGC-7901 cells. si-SMAD4 transfection weakened cell apoptosis and accelerated cell proliferation. Furthermore, FKB reversed the change in apoptotic and cell cycle-related proteins induced by si-SMAD4. A nude mouse tumorigenesis model was constructed, which was treated by FKB. In the nude mouse tumorigenesis model, FKB activated the TSPAN12 expression and TGF-β1/SMAD4 pathway. Also, FKB treatment prolonged the survival time of nude mice and lowered tumor weight. iNOS and CD86 expression was significantly enhanced, and Arg-1 and CD206 expression was significantly decreased in THP-1 cells cultured in conditioned media from FKB-treated SGC-7901 cells. Additionally, FKB-treated SGC-7901 cells weakened macrophage migration. Collectively, this evidence suggested that FKB accelerated apoptosis and suppressed the proliferation of gastric cancer cells and attenuated M2 macrophage polarization, thereby exerting an anticancer effect on gastric cancer.
format Online
Article
Text
id pubmed-9308533
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-93085332022-07-24 Flavokawain B Weakens Gastric Cancer Progression via the TGF-β1/SMAD4 Pathway and Attenuates M2 Macrophage Polarization Zhu, Yongzhao Fan, Weining Wang, Yuanzhen Ding, Huan Yang, Shaoqi He, Fang J Immunol Res Research Article This study was designed to observe the treatment effects of flavokawain B (FKB) on gastric cancer both in SGC-7901 cells and nude mice. When SGC-7901 cells were exposed to 10 μg/mL FKB, cellular proliferative and apoptotic capacities and cell cycle were detected utilizing CCK-8 and flow cytometry assays. The results showed that FKB treatment induced cell apoptosis and G2/M arrest and suppressed cell proliferation for SGC-7901 cells. Western blot results showed that FKB upregulated proapoptotic proteins as well as downregulated antiapoptotic and cell cycle-related proteins in SGC-7901 cells. SMAD4, TGF-β1, and TSPAN12 proteins were tested in FKB-induced SGC-7901 cells. Following exposure to FKB, SMAD4, TGF-β1, and TSPAN12 expression was augmented in SGC-7901 cells. si-SMAD4 transfection weakened cell apoptosis and accelerated cell proliferation. Furthermore, FKB reversed the change in apoptotic and cell cycle-related proteins induced by si-SMAD4. A nude mouse tumorigenesis model was constructed, which was treated by FKB. In the nude mouse tumorigenesis model, FKB activated the TSPAN12 expression and TGF-β1/SMAD4 pathway. Also, FKB treatment prolonged the survival time of nude mice and lowered tumor weight. iNOS and CD86 expression was significantly enhanced, and Arg-1 and CD206 expression was significantly decreased in THP-1 cells cultured in conditioned media from FKB-treated SGC-7901 cells. Additionally, FKB-treated SGC-7901 cells weakened macrophage migration. Collectively, this evidence suggested that FKB accelerated apoptosis and suppressed the proliferation of gastric cancer cells and attenuated M2 macrophage polarization, thereby exerting an anticancer effect on gastric cancer. Hindawi 2022-07-16 /pmc/articles/PMC9308533/ /pubmed/35879950 http://dx.doi.org/10.1155/2022/4903333 Text en Copyright © 2022 Yongzhao Zhu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhu, Yongzhao
Fan, Weining
Wang, Yuanzhen
Ding, Huan
Yang, Shaoqi
He, Fang
Flavokawain B Weakens Gastric Cancer Progression via the TGF-β1/SMAD4 Pathway and Attenuates M2 Macrophage Polarization
title Flavokawain B Weakens Gastric Cancer Progression via the TGF-β1/SMAD4 Pathway and Attenuates M2 Macrophage Polarization
title_full Flavokawain B Weakens Gastric Cancer Progression via the TGF-β1/SMAD4 Pathway and Attenuates M2 Macrophage Polarization
title_fullStr Flavokawain B Weakens Gastric Cancer Progression via the TGF-β1/SMAD4 Pathway and Attenuates M2 Macrophage Polarization
title_full_unstemmed Flavokawain B Weakens Gastric Cancer Progression via the TGF-β1/SMAD4 Pathway and Attenuates M2 Macrophage Polarization
title_short Flavokawain B Weakens Gastric Cancer Progression via the TGF-β1/SMAD4 Pathway and Attenuates M2 Macrophage Polarization
title_sort flavokawain b weakens gastric cancer progression via the tgf-β1/smad4 pathway and attenuates m2 macrophage polarization
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308533/
https://www.ncbi.nlm.nih.gov/pubmed/35879950
http://dx.doi.org/10.1155/2022/4903333
work_keys_str_mv AT zhuyongzhao flavokawainbweakensgastriccancerprogressionviathetgfb1smad4pathwayandattenuatesm2macrophagepolarization
AT fanweining flavokawainbweakensgastriccancerprogressionviathetgfb1smad4pathwayandattenuatesm2macrophagepolarization
AT wangyuanzhen flavokawainbweakensgastriccancerprogressionviathetgfb1smad4pathwayandattenuatesm2macrophagepolarization
AT dinghuan flavokawainbweakensgastriccancerprogressionviathetgfb1smad4pathwayandattenuatesm2macrophagepolarization
AT yangshaoqi flavokawainbweakensgastriccancerprogressionviathetgfb1smad4pathwayandattenuatesm2macrophagepolarization
AT hefang flavokawainbweakensgastriccancerprogressionviathetgfb1smad4pathwayandattenuatesm2macrophagepolarization