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Icariin enhances the chemosensitivity of cisplatin‑resistant ovarian cancer cells by suppressing autophagy via activation of the AKT/mTOR/ATG5 pathway
Icariin is a flavonoid derived from Epimedium sagittatum, and has a wide range of biological and pharmacological effects; however, little is known regarding its effect on drug-resistant ovarian cancer and the signal transduction pathways underlying the regulation of apoptosis and autophagy. The pres...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521925/ https://www.ncbi.nlm.nih.gov/pubmed/31081049 http://dx.doi.org/10.3892/ijo.2019.4785 |
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author | Jiang, Shaoyan Chang, Hong Deng, Shaojie Fan, Danyi |
author_facet | Jiang, Shaoyan Chang, Hong Deng, Shaojie Fan, Danyi |
author_sort | Jiang, Shaoyan |
collection | PubMed |
description | Icariin is a flavonoid derived from Epimedium sagittatum, and has a wide range of biological and pharmacological effects; however, little is known regarding its effect on drug-resistant ovarian cancer and the signal transduction pathways underlying the regulation of apoptosis and autophagy. The present study aimed to investigate the re-sensitization effects of icariin exerted on an ovarian cancer cell line. Autophagy was analyzed in a SKVCR cell line that had been treated with icariin. We investigated the sensitivity of SKVCR cells to cisplatin, as well as the effects of an autophagy agonist (rapamycin) on autophagy, apoptosis, and the protein kinase B (AKT) signaling pathway. Finally, the mechanism underlying the effects of autophagy-related (ATG) protein ATG5 overexpression on autophagy, apoptosis and AKT signaling in SKVCR cells were determined. The results revealed that treatment with icariin inhibited cell viability and autophagy, but promoted G0/G1 phase cell cycle arrest and apoptosis as determined by Cell Counting Kit-8, immunofluorescence and flow cytometry assays, respectively. Icariin reduced the resistance of SKVCR cells to cisplatin in vitro by inducing G1/S cell cycle transition, apoptosis and inhibiting autophagy. Furthermore, enhanced autophagy induced by rapamycin treatment or overexpression of ATG5 partially reversed the effect of icariin on cisplatin resistance and autophagy in SKVCR cells. At the molecular level, rapamycin treatment or overexpression of ATG5 reversed the effects of icariin on the expression of autophagy-associated proteins, including microtubule-associated protein 1 light chain 3β, Beclin-1, ATG5 and p62, and the AKT/mammalian target of rapamycin (mTOR) pathway. Collectively, our results suggested that icariin enhances the chemosensitivity of SKVCR cells by suppressing autophagy via activation of the AKT/mTOR signaling pathway. |
format | Online Article Text |
id | pubmed-6521925 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-65219252019-06-18 Icariin enhances the chemosensitivity of cisplatin‑resistant ovarian cancer cells by suppressing autophagy via activation of the AKT/mTOR/ATG5 pathway Jiang, Shaoyan Chang, Hong Deng, Shaojie Fan, Danyi Int J Oncol Articles Icariin is a flavonoid derived from Epimedium sagittatum, and has a wide range of biological and pharmacological effects; however, little is known regarding its effect on drug-resistant ovarian cancer and the signal transduction pathways underlying the regulation of apoptosis and autophagy. The present study aimed to investigate the re-sensitization effects of icariin exerted on an ovarian cancer cell line. Autophagy was analyzed in a SKVCR cell line that had been treated with icariin. We investigated the sensitivity of SKVCR cells to cisplatin, as well as the effects of an autophagy agonist (rapamycin) on autophagy, apoptosis, and the protein kinase B (AKT) signaling pathway. Finally, the mechanism underlying the effects of autophagy-related (ATG) protein ATG5 overexpression on autophagy, apoptosis and AKT signaling in SKVCR cells were determined. The results revealed that treatment with icariin inhibited cell viability and autophagy, but promoted G0/G1 phase cell cycle arrest and apoptosis as determined by Cell Counting Kit-8, immunofluorescence and flow cytometry assays, respectively. Icariin reduced the resistance of SKVCR cells to cisplatin in vitro by inducing G1/S cell cycle transition, apoptosis and inhibiting autophagy. Furthermore, enhanced autophagy induced by rapamycin treatment or overexpression of ATG5 partially reversed the effect of icariin on cisplatin resistance and autophagy in SKVCR cells. At the molecular level, rapamycin treatment or overexpression of ATG5 reversed the effects of icariin on the expression of autophagy-associated proteins, including microtubule-associated protein 1 light chain 3β, Beclin-1, ATG5 and p62, and the AKT/mammalian target of rapamycin (mTOR) pathway. Collectively, our results suggested that icariin enhances the chemosensitivity of SKVCR cells by suppressing autophagy via activation of the AKT/mTOR signaling pathway. D.A. Spandidos 2019-04-15 /pmc/articles/PMC6521925/ /pubmed/31081049 http://dx.doi.org/10.3892/ijo.2019.4785 Text en Copyright: © Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Jiang, Shaoyan Chang, Hong Deng, Shaojie Fan, Danyi Icariin enhances the chemosensitivity of cisplatin‑resistant ovarian cancer cells by suppressing autophagy via activation of the AKT/mTOR/ATG5 pathway |
title | Icariin enhances the chemosensitivity of cisplatin‑resistant ovarian cancer cells by suppressing autophagy via activation of the AKT/mTOR/ATG5 pathway |
title_full | Icariin enhances the chemosensitivity of cisplatin‑resistant ovarian cancer cells by suppressing autophagy via activation of the AKT/mTOR/ATG5 pathway |
title_fullStr | Icariin enhances the chemosensitivity of cisplatin‑resistant ovarian cancer cells by suppressing autophagy via activation of the AKT/mTOR/ATG5 pathway |
title_full_unstemmed | Icariin enhances the chemosensitivity of cisplatin‑resistant ovarian cancer cells by suppressing autophagy via activation of the AKT/mTOR/ATG5 pathway |
title_short | Icariin enhances the chemosensitivity of cisplatin‑resistant ovarian cancer cells by suppressing autophagy via activation of the AKT/mTOR/ATG5 pathway |
title_sort | icariin enhances the chemosensitivity of cisplatin‑resistant ovarian cancer cells by suppressing autophagy via activation of the akt/mtor/atg5 pathway |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521925/ https://www.ncbi.nlm.nih.gov/pubmed/31081049 http://dx.doi.org/10.3892/ijo.2019.4785 |
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