Cargando…

Astragali radix total flavonoid synergizes cisplatin to inhibit proliferation and enhances the chemosensitivity of laryngeal squamous cell carcinoma

Laryngeal squamous cell carcinoma (LSCC) is the most common head and neck cancer. Astragali radix extracts play crucial roles in the regulation of cancer progression. However, the role of Astragali radix extracts in LSCC and the related mechanisms remains unclear. Here, we evaluated the inhibitory e...

Descripción completa

Detalles Bibliográficos
Autores principales: Cui, Jiajia, Zheng, Xiwang, Yang, Dongli, Hu, Yinghuan, An, Changming, Bo, Yunfeng, Li, Huizheng, Zhang, Yuliang, Niu, Min, Xue, Xuting, Lu, Yan, Tang, Yemei, Yin, Hongyu, Li, Zhenyu, Gao, Wei, Wu, Yongyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9069756/
https://www.ncbi.nlm.nih.gov/pubmed/35527911
http://dx.doi.org/10.1039/c9ra04701h
_version_ 1784700498615468032
author Cui, Jiajia
Zheng, Xiwang
Yang, Dongli
Hu, Yinghuan
An, Changming
Bo, Yunfeng
Li, Huizheng
Zhang, Yuliang
Niu, Min
Xue, Xuting
Lu, Yan
Tang, Yemei
Yin, Hongyu
Li, Zhenyu
Gao, Wei
Wu, Yongyan
author_facet Cui, Jiajia
Zheng, Xiwang
Yang, Dongli
Hu, Yinghuan
An, Changming
Bo, Yunfeng
Li, Huizheng
Zhang, Yuliang
Niu, Min
Xue, Xuting
Lu, Yan
Tang, Yemei
Yin, Hongyu
Li, Zhenyu
Gao, Wei
Wu, Yongyan
author_sort Cui, Jiajia
collection PubMed
description Laryngeal squamous cell carcinoma (LSCC) is the most common head and neck cancer. Astragali radix extracts play crucial roles in the regulation of cancer progression. However, the role of Astragali radix extracts in LSCC and the related mechanisms remains unclear. Here, we evaluated the inhibitory effects of the combined use of Astragali radix total flavonoid (TFA) and cisplatin (CDDP) on an LSCC mouse model by pharmacodynamics. Ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed to define the prototype of TFA in vivo. The potential drug targets were identified through the integrative analysis of LSCC microarrays, RNA sequencing data and the main bioactive component of TFA. Furthermore, a protein–protein interaction network, compound–target network and target–pathway network were constructed based on the prototype and potential drug targets to identify the main targets and pathways. Animal experiments showed that TFA has significant synergistic antitumor activity with cisplatin and attenuates the nephrotoxicity caused by CDDP chemotherapy, improving the survival of LSCC-bearing mice. Using UPLC-MS/MS, we identified 8 constituents of TFA in experimental mice serum: formononetin, ononin, calycosin, calycosin-7-O-β-D-glucoside, 7,2′-dihydroxy-3′,4′-dimethoxyisoflavan, 7,2′-dihydroxy-3′,4′-dimethoxyisoflavaneglucoside, 3-hydroxy-9,10-dimethoxypterocarpan and 9,10-dimethoxyptercarpan-3-O-β-d-glucoside. Integrative analysis predicted 19 target genes for TFA constituents, and the target genes were mainly involved in the EGFR-related cancer signaling, metabolism and oxidative stress. Collectively, these findings highlight the role of TFA in the regulation of LSCC and provide potential targets for a high-efficiency and low-toxicity therapeutic strategy of LSCC.
format Online
Article
Text
id pubmed-9069756
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher The Royal Society of Chemistry
record_format MEDLINE/PubMed
spelling pubmed-90697562022-05-05 Astragali radix total flavonoid synergizes cisplatin to inhibit proliferation and enhances the chemosensitivity of laryngeal squamous cell carcinoma Cui, Jiajia Zheng, Xiwang Yang, Dongli Hu, Yinghuan An, Changming Bo, Yunfeng Li, Huizheng Zhang, Yuliang Niu, Min Xue, Xuting Lu, Yan Tang, Yemei Yin, Hongyu Li, Zhenyu Gao, Wei Wu, Yongyan RSC Adv Chemistry Laryngeal squamous cell carcinoma (LSCC) is the most common head and neck cancer. Astragali radix extracts play crucial roles in the regulation of cancer progression. However, the role of Astragali radix extracts in LSCC and the related mechanisms remains unclear. Here, we evaluated the inhibitory effects of the combined use of Astragali radix total flavonoid (TFA) and cisplatin (CDDP) on an LSCC mouse model by pharmacodynamics. Ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed to define the prototype of TFA in vivo. The potential drug targets were identified through the integrative analysis of LSCC microarrays, RNA sequencing data and the main bioactive component of TFA. Furthermore, a protein–protein interaction network, compound–target network and target–pathway network were constructed based on the prototype and potential drug targets to identify the main targets and pathways. Animal experiments showed that TFA has significant synergistic antitumor activity with cisplatin and attenuates the nephrotoxicity caused by CDDP chemotherapy, improving the survival of LSCC-bearing mice. Using UPLC-MS/MS, we identified 8 constituents of TFA in experimental mice serum: formononetin, ononin, calycosin, calycosin-7-O-β-D-glucoside, 7,2′-dihydroxy-3′,4′-dimethoxyisoflavan, 7,2′-dihydroxy-3′,4′-dimethoxyisoflavaneglucoside, 3-hydroxy-9,10-dimethoxypterocarpan and 9,10-dimethoxyptercarpan-3-O-β-d-glucoside. Integrative analysis predicted 19 target genes for TFA constituents, and the target genes were mainly involved in the EGFR-related cancer signaling, metabolism and oxidative stress. Collectively, these findings highlight the role of TFA in the regulation of LSCC and provide potential targets for a high-efficiency and low-toxicity therapeutic strategy of LSCC. The Royal Society of Chemistry 2019-08-07 /pmc/articles/PMC9069756/ /pubmed/35527911 http://dx.doi.org/10.1039/c9ra04701h Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Cui, Jiajia
Zheng, Xiwang
Yang, Dongli
Hu, Yinghuan
An, Changming
Bo, Yunfeng
Li, Huizheng
Zhang, Yuliang
Niu, Min
Xue, Xuting
Lu, Yan
Tang, Yemei
Yin, Hongyu
Li, Zhenyu
Gao, Wei
Wu, Yongyan
Astragali radix total flavonoid synergizes cisplatin to inhibit proliferation and enhances the chemosensitivity of laryngeal squamous cell carcinoma
title Astragali radix total flavonoid synergizes cisplatin to inhibit proliferation and enhances the chemosensitivity of laryngeal squamous cell carcinoma
title_full Astragali radix total flavonoid synergizes cisplatin to inhibit proliferation and enhances the chemosensitivity of laryngeal squamous cell carcinoma
title_fullStr Astragali radix total flavonoid synergizes cisplatin to inhibit proliferation and enhances the chemosensitivity of laryngeal squamous cell carcinoma
title_full_unstemmed Astragali radix total flavonoid synergizes cisplatin to inhibit proliferation and enhances the chemosensitivity of laryngeal squamous cell carcinoma
title_short Astragali radix total flavonoid synergizes cisplatin to inhibit proliferation and enhances the chemosensitivity of laryngeal squamous cell carcinoma
title_sort astragali radix total flavonoid synergizes cisplatin to inhibit proliferation and enhances the chemosensitivity of laryngeal squamous cell carcinoma
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9069756/
https://www.ncbi.nlm.nih.gov/pubmed/35527911
http://dx.doi.org/10.1039/c9ra04701h
work_keys_str_mv AT cuijiajia astragaliradixtotalflavonoidsynergizescisplatintoinhibitproliferationandenhancesthechemosensitivityoflaryngealsquamouscellcarcinoma
AT zhengxiwang astragaliradixtotalflavonoidsynergizescisplatintoinhibitproliferationandenhancesthechemosensitivityoflaryngealsquamouscellcarcinoma
AT yangdongli astragaliradixtotalflavonoidsynergizescisplatintoinhibitproliferationandenhancesthechemosensitivityoflaryngealsquamouscellcarcinoma
AT huyinghuan astragaliradixtotalflavonoidsynergizescisplatintoinhibitproliferationandenhancesthechemosensitivityoflaryngealsquamouscellcarcinoma
AT anchangming astragaliradixtotalflavonoidsynergizescisplatintoinhibitproliferationandenhancesthechemosensitivityoflaryngealsquamouscellcarcinoma
AT boyunfeng astragaliradixtotalflavonoidsynergizescisplatintoinhibitproliferationandenhancesthechemosensitivityoflaryngealsquamouscellcarcinoma
AT lihuizheng astragaliradixtotalflavonoidsynergizescisplatintoinhibitproliferationandenhancesthechemosensitivityoflaryngealsquamouscellcarcinoma
AT zhangyuliang astragaliradixtotalflavonoidsynergizescisplatintoinhibitproliferationandenhancesthechemosensitivityoflaryngealsquamouscellcarcinoma
AT niumin astragaliradixtotalflavonoidsynergizescisplatintoinhibitproliferationandenhancesthechemosensitivityoflaryngealsquamouscellcarcinoma
AT xuexuting astragaliradixtotalflavonoidsynergizescisplatintoinhibitproliferationandenhancesthechemosensitivityoflaryngealsquamouscellcarcinoma
AT luyan astragaliradixtotalflavonoidsynergizescisplatintoinhibitproliferationandenhancesthechemosensitivityoflaryngealsquamouscellcarcinoma
AT tangyemei astragaliradixtotalflavonoidsynergizescisplatintoinhibitproliferationandenhancesthechemosensitivityoflaryngealsquamouscellcarcinoma
AT yinhongyu astragaliradixtotalflavonoidsynergizescisplatintoinhibitproliferationandenhancesthechemosensitivityoflaryngealsquamouscellcarcinoma
AT lizhenyu astragaliradixtotalflavonoidsynergizescisplatintoinhibitproliferationandenhancesthechemosensitivityoflaryngealsquamouscellcarcinoma
AT gaowei astragaliradixtotalflavonoidsynergizescisplatintoinhibitproliferationandenhancesthechemosensitivityoflaryngealsquamouscellcarcinoma
AT wuyongyan astragaliradixtotalflavonoidsynergizescisplatintoinhibitproliferationandenhancesthechemosensitivityoflaryngealsquamouscellcarcinoma