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Wogonin increases gemcitabine sensitivity in pancreatic cancer by inhibiting Akt pathway

Pancreatic cancer has a high degree of malignancy and a low 5-year survival rate, and drug resistance is one of the main factors leading to poor prognosis of pancreatic cancer. Wogonin is a flavonoid drug isolated from Scutellaria baicalensis, which has certain antitumor activity. Hence the purpose...

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Autores principales: Zhang, Tianli, Liu, Mengmeng, Liu, Qing, Xiao, Gary Guishan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9816391/
https://www.ncbi.nlm.nih.gov/pubmed/36618921
http://dx.doi.org/10.3389/fphar.2022.1068855
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author Zhang, Tianli
Liu, Mengmeng
Liu, Qing
Xiao, Gary Guishan
author_facet Zhang, Tianli
Liu, Mengmeng
Liu, Qing
Xiao, Gary Guishan
author_sort Zhang, Tianli
collection PubMed
description Pancreatic cancer has a high degree of malignancy and a low 5-year survival rate, and drug resistance is one of the main factors leading to poor prognosis of pancreatic cancer. Wogonin is a flavonoid drug isolated from Scutellaria baicalensis, which has certain antitumor activity. Hence the purpose of this study was to investigate whether wogonin can be used to enhance the sensitivity of pancreatic cancer to gemcitabine chemotherapy, and investigate its possible sensitization mechanism. In vitro, MTT assay showed that wogonin increased gemcitabine cytotoxicity in gemcitabine-resistant pancreatic cancer cells. In vivo, Wogonin combined with gemcitabine was found to inhibit tumor growth in orthotopic pancreatic cancer mouse model. In order to explore the sensitization mechanism, the differentially expressed genes (DEGs) of the gemcitabine-resistant cell line Panc-1 and the gemcitabine-sensitive cell line Bxpc-3 were screened through the GEO database, and 15 differentially expressed genes were obtained by intersecting with the potential targets of wogonin. Gene Ontology and KEGG enrichment analysis was performed. Bioinformatics results predicted that wogonin promoted pancreatic cancer cell apoptosis by inhibiting protein kinase B (Akt) signaling, thereby enhancing the sensitivity of gemcitabine to Pancreatic cancer. The above results were also verified by flow cytometry and Western blotting experiments. In conclusion, wogonin may enhance the sensitivity of gemcitabine by inhibiting Akt pathway.
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spelling pubmed-98163912023-01-07 Wogonin increases gemcitabine sensitivity in pancreatic cancer by inhibiting Akt pathway Zhang, Tianli Liu, Mengmeng Liu, Qing Xiao, Gary Guishan Front Pharmacol Pharmacology Pancreatic cancer has a high degree of malignancy and a low 5-year survival rate, and drug resistance is one of the main factors leading to poor prognosis of pancreatic cancer. Wogonin is a flavonoid drug isolated from Scutellaria baicalensis, which has certain antitumor activity. Hence the purpose of this study was to investigate whether wogonin can be used to enhance the sensitivity of pancreatic cancer to gemcitabine chemotherapy, and investigate its possible sensitization mechanism. In vitro, MTT assay showed that wogonin increased gemcitabine cytotoxicity in gemcitabine-resistant pancreatic cancer cells. In vivo, Wogonin combined with gemcitabine was found to inhibit tumor growth in orthotopic pancreatic cancer mouse model. In order to explore the sensitization mechanism, the differentially expressed genes (DEGs) of the gemcitabine-resistant cell line Panc-1 and the gemcitabine-sensitive cell line Bxpc-3 were screened through the GEO database, and 15 differentially expressed genes were obtained by intersecting with the potential targets of wogonin. Gene Ontology and KEGG enrichment analysis was performed. Bioinformatics results predicted that wogonin promoted pancreatic cancer cell apoptosis by inhibiting protein kinase B (Akt) signaling, thereby enhancing the sensitivity of gemcitabine to Pancreatic cancer. The above results were also verified by flow cytometry and Western blotting experiments. In conclusion, wogonin may enhance the sensitivity of gemcitabine by inhibiting Akt pathway. Frontiers Media S.A. 2022-12-23 /pmc/articles/PMC9816391/ /pubmed/36618921 http://dx.doi.org/10.3389/fphar.2022.1068855 Text en Copyright © 2022 Zhang, Liu, Liu and Xiao. 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 Pharmacology
Zhang, Tianli
Liu, Mengmeng
Liu, Qing
Xiao, Gary Guishan
Wogonin increases gemcitabine sensitivity in pancreatic cancer by inhibiting Akt pathway
title Wogonin increases gemcitabine sensitivity in pancreatic cancer by inhibiting Akt pathway
title_full Wogonin increases gemcitabine sensitivity in pancreatic cancer by inhibiting Akt pathway
title_fullStr Wogonin increases gemcitabine sensitivity in pancreatic cancer by inhibiting Akt pathway
title_full_unstemmed Wogonin increases gemcitabine sensitivity in pancreatic cancer by inhibiting Akt pathway
title_short Wogonin increases gemcitabine sensitivity in pancreatic cancer by inhibiting Akt pathway
title_sort wogonin increases gemcitabine sensitivity in pancreatic cancer by inhibiting akt pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9816391/
https://www.ncbi.nlm.nih.gov/pubmed/36618921
http://dx.doi.org/10.3389/fphar.2022.1068855
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