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Shikonin Mediates Apoptosis through G Protein-Coupled Estrogen Receptor of Ovarian Cancer Cells
This study was intended to establish the predictive target of Shikonin (SK) against ovarian cancer using network pharmacology and to clarify the potential mechanism of SK in promoting apoptosis in ovarian cancer. Cell Counting Kit-8 assay, plate clone assays, LDH assay, flow cytometric analysis of A...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9556250/ https://www.ncbi.nlm.nih.gov/pubmed/36248433 http://dx.doi.org/10.1155/2022/6517732 |
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author | Liu, Xinyue Yang, Yao Tang, Xuefei Guo, Li Tang, Xinhui Zhu, Ting Zhao, Tiannan Zhang, Weina Zhang, Ping |
author_facet | Liu, Xinyue Yang, Yao Tang, Xuefei Guo, Li Tang, Xinhui Zhu, Ting Zhao, Tiannan Zhang, Weina Zhang, Ping |
author_sort | Liu, Xinyue |
collection | PubMed |
description | This study was intended to establish the predictive target of Shikonin (SK) against ovarian cancer using network pharmacology and to clarify the potential mechanism of SK in promoting apoptosis in ovarian cancer. Cell Counting Kit-8 assay, plate clone assays, LDH assay, flow cytometric analysis of Annexin V-fluorescein isothiocyanate/propidium iodide staining, and western blotting were used to assess the effect of SK on apoptosis of ovarian cancer cell lines (SKOV3 and A2780). Pharmacodynamic targets were used to predict the targets of SK and ovarian cancer. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analyses were used to analyze the biological functions and signal pathways of these targets. SK promoted apoptosis in ovarian epithelioid adenocarcinoma cells. SK-ovarian cancer pharmacodynamic target analysis screened 17 related genes. GO and KEGG analyses showed that SK affected the estrogen signaling pathway. SK inhibited the expression of GPER in SKOV3 and A2780 cells and downregulated the expression of EGFR, p-EGFR, PI3K, and p-AKT in a concentration-dependent manner. The apoptosis-promoting effect of SK was enhanced by GPER-specific agonist G1 and inhibited by the specific inhibitor G15. The expression of EGFR, p-EGFR, PI3K, and p-AKT was decreased by G1 and reversed by G15. SK also inhibited tumor growth in the SKOV3 xenograft model, and it acted synergistically with G1. However, the effect can be attenuated by G15 in vivo. In summary, SK may affect the apoptosis of ovarian cancer cells through GPER/EGFR/PI3K/AKT, and GPER may be a key target of SK in ovarian cancer cell apoptosis. |
format | Online Article Text |
id | pubmed-9556250 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-95562502022-10-13 Shikonin Mediates Apoptosis through G Protein-Coupled Estrogen Receptor of Ovarian Cancer Cells Liu, Xinyue Yang, Yao Tang, Xuefei Guo, Li Tang, Xinhui Zhu, Ting Zhao, Tiannan Zhang, Weina Zhang, Ping Evid Based Complement Alternat Med Research Article This study was intended to establish the predictive target of Shikonin (SK) against ovarian cancer using network pharmacology and to clarify the potential mechanism of SK in promoting apoptosis in ovarian cancer. Cell Counting Kit-8 assay, plate clone assays, LDH assay, flow cytometric analysis of Annexin V-fluorescein isothiocyanate/propidium iodide staining, and western blotting were used to assess the effect of SK on apoptosis of ovarian cancer cell lines (SKOV3 and A2780). Pharmacodynamic targets were used to predict the targets of SK and ovarian cancer. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analyses were used to analyze the biological functions and signal pathways of these targets. SK promoted apoptosis in ovarian epithelioid adenocarcinoma cells. SK-ovarian cancer pharmacodynamic target analysis screened 17 related genes. GO and KEGG analyses showed that SK affected the estrogen signaling pathway. SK inhibited the expression of GPER in SKOV3 and A2780 cells and downregulated the expression of EGFR, p-EGFR, PI3K, and p-AKT in a concentration-dependent manner. The apoptosis-promoting effect of SK was enhanced by GPER-specific agonist G1 and inhibited by the specific inhibitor G15. The expression of EGFR, p-EGFR, PI3K, and p-AKT was decreased by G1 and reversed by G15. SK also inhibited tumor growth in the SKOV3 xenograft model, and it acted synergistically with G1. However, the effect can be attenuated by G15 in vivo. In summary, SK may affect the apoptosis of ovarian cancer cells through GPER/EGFR/PI3K/AKT, and GPER may be a key target of SK in ovarian cancer cell apoptosis. Hindawi 2022-10-05 /pmc/articles/PMC9556250/ /pubmed/36248433 http://dx.doi.org/10.1155/2022/6517732 Text en Copyright © 2022 Xinyue Liu 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 Liu, Xinyue Yang, Yao Tang, Xuefei Guo, Li Tang, Xinhui Zhu, Ting Zhao, Tiannan Zhang, Weina Zhang, Ping Shikonin Mediates Apoptosis through G Protein-Coupled Estrogen Receptor of Ovarian Cancer Cells |
title | Shikonin Mediates Apoptosis through G Protein-Coupled Estrogen Receptor of Ovarian Cancer Cells |
title_full | Shikonin Mediates Apoptosis through G Protein-Coupled Estrogen Receptor of Ovarian Cancer Cells |
title_fullStr | Shikonin Mediates Apoptosis through G Protein-Coupled Estrogen Receptor of Ovarian Cancer Cells |
title_full_unstemmed | Shikonin Mediates Apoptosis through G Protein-Coupled Estrogen Receptor of Ovarian Cancer Cells |
title_short | Shikonin Mediates Apoptosis through G Protein-Coupled Estrogen Receptor of Ovarian Cancer Cells |
title_sort | shikonin mediates apoptosis through g protein-coupled estrogen receptor of ovarian cancer cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9556250/ https://www.ncbi.nlm.nih.gov/pubmed/36248433 http://dx.doi.org/10.1155/2022/6517732 |
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