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Compound Kushen injection inhibits EMT of gastric cancer cells via the PI3K/AKT pathway

BACKGROUND: The effective components contained in compound Kushen injection (CKI) and the genes and signalling pathways related to gastric cancer (GC) were analyzed through the network pharmacology method of traditional Chinese medicine, and various possible mechanisms by which CKI affects the proli...

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Autores principales: Li, Luo, Wang, Keshan, Liu, Zhenguo, Lü, Yajuan, Wang, Congcong, Yi, Xuefei, Guo, Jianping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121642/
https://www.ncbi.nlm.nih.gov/pubmed/35590327
http://dx.doi.org/10.1186/s12957-022-02609-y
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author Li, Luo
Wang, Keshan
Liu, Zhenguo
Lü, Yajuan
Wang, Congcong
Yi, Xuefei
Guo, Jianping
author_facet Li, Luo
Wang, Keshan
Liu, Zhenguo
Lü, Yajuan
Wang, Congcong
Yi, Xuefei
Guo, Jianping
author_sort Li, Luo
collection PubMed
description BACKGROUND: The effective components contained in compound Kushen injection (CKI) and the genes and signalling pathways related to gastric cancer (GC) were analyzed through the network pharmacology method of traditional Chinese medicine, and various possible mechanisms by which CKI affects the proliferation, differentiation, survival, and metastasis of GC cells were discussed. The PI3K/AKT signalling pathway is considered to be one of the most important pathways targeted by CKI in the regulation of GC cells. The implementation of related cell experiments also confirmed the information we revealed. METHODS: Effective drug components of Kushen and Baituling in CKI were identified from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). Genes related to GC were identified using the GENECARD and OMIM databases. The common target genes related to the effective components of the drug and GC were identified using the intersection method and visualized using software. A protein–protein interaction network (PPI) was established using STRING online software to confirm the key genes. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the key pathways of CKI in GC treatment. BGC-803 and MKN-28 GC cells were used to verify the signalling pathway. Cell proliferation, apoptosis, migration ability, and invasion ability were assessed using CCK8, flow cytometry, scratch, and transwell assays. Immunofluorescence assays and western blotting were used to detect the expression of related proteins. RESULTS: CKI regulated GC cells through 35 effective drug components of GC-related target genes. In total, 194 genes were common targets of CKI and GC. The most significant function of the enriched genes was DNA-binding transcription activator activity as demonstrated by GO enrichment analysis. The metabolic pathway with the highest enrichment was the PI3K/AKT signalling pathway as demonstrated by KEGG enrichment analysis. Our cell experimental evidence also shows that CKI inhibits GC cell growth and migration and induce GC cell apoptosis. In addition, CKI inhibits the EMT process in GC cells through the PI3K/AKT signalling pathway. CONCLUSION: AKT1 is a key gene for CKI treatment of GC. CKI inhibited GC cell growth and migration and induced GC cell apoptosis. In addition, CKI regulated the EMT process in GC cells through the PI3K/AKT signalling pathway.
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spelling pubmed-91216422022-05-21 Compound Kushen injection inhibits EMT of gastric cancer cells via the PI3K/AKT pathway Li, Luo Wang, Keshan Liu, Zhenguo Lü, Yajuan Wang, Congcong Yi, Xuefei Guo, Jianping World J Surg Oncol Research BACKGROUND: The effective components contained in compound Kushen injection (CKI) and the genes and signalling pathways related to gastric cancer (GC) were analyzed through the network pharmacology method of traditional Chinese medicine, and various possible mechanisms by which CKI affects the proliferation, differentiation, survival, and metastasis of GC cells were discussed. The PI3K/AKT signalling pathway is considered to be one of the most important pathways targeted by CKI in the regulation of GC cells. The implementation of related cell experiments also confirmed the information we revealed. METHODS: Effective drug components of Kushen and Baituling in CKI were identified from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). Genes related to GC were identified using the GENECARD and OMIM databases. The common target genes related to the effective components of the drug and GC were identified using the intersection method and visualized using software. A protein–protein interaction network (PPI) was established using STRING online software to confirm the key genes. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the key pathways of CKI in GC treatment. BGC-803 and MKN-28 GC cells were used to verify the signalling pathway. Cell proliferation, apoptosis, migration ability, and invasion ability were assessed using CCK8, flow cytometry, scratch, and transwell assays. Immunofluorescence assays and western blotting were used to detect the expression of related proteins. RESULTS: CKI regulated GC cells through 35 effective drug components of GC-related target genes. In total, 194 genes were common targets of CKI and GC. The most significant function of the enriched genes was DNA-binding transcription activator activity as demonstrated by GO enrichment analysis. The metabolic pathway with the highest enrichment was the PI3K/AKT signalling pathway as demonstrated by KEGG enrichment analysis. Our cell experimental evidence also shows that CKI inhibits GC cell growth and migration and induce GC cell apoptosis. In addition, CKI inhibits the EMT process in GC cells through the PI3K/AKT signalling pathway. CONCLUSION: AKT1 is a key gene for CKI treatment of GC. CKI inhibited GC cell growth and migration and induced GC cell apoptosis. In addition, CKI regulated the EMT process in GC cells through the PI3K/AKT signalling pathway. BioMed Central 2022-05-20 /pmc/articles/PMC9121642/ /pubmed/35590327 http://dx.doi.org/10.1186/s12957-022-02609-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Li, Luo
Wang, Keshan
Liu, Zhenguo
Lü, Yajuan
Wang, Congcong
Yi, Xuefei
Guo, Jianping
Compound Kushen injection inhibits EMT of gastric cancer cells via the PI3K/AKT pathway
title Compound Kushen injection inhibits EMT of gastric cancer cells via the PI3K/AKT pathway
title_full Compound Kushen injection inhibits EMT of gastric cancer cells via the PI3K/AKT pathway
title_fullStr Compound Kushen injection inhibits EMT of gastric cancer cells via the PI3K/AKT pathway
title_full_unstemmed Compound Kushen injection inhibits EMT of gastric cancer cells via the PI3K/AKT pathway
title_short Compound Kushen injection inhibits EMT of gastric cancer cells via the PI3K/AKT pathway
title_sort compound kushen injection inhibits emt of gastric cancer cells via the pi3k/akt pathway
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121642/
https://www.ncbi.nlm.nih.gov/pubmed/35590327
http://dx.doi.org/10.1186/s12957-022-02609-y
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