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Aspirin inhibits tumor progression and enhances cisplatin sensitivity in epithelial ovarian cancer

BACKGROUND: Ovarian cancer is the most common gynecological malignancy and is difficult to manage due to the emergence of resistance to various chemotherapeutic drugs. New efforts are urgently awaited. Aspirin, which is traditionally considered a nonsteroidal anti-inflammatory drug (NSAID), has been...

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Autores principales: Guo, Jianfeng, Zhu, Yapei, Yu, Lili, Li, Yuan, Guo, Jing, Cai, Jing, Liu, Lin, Wang, Zehua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340904/
https://www.ncbi.nlm.nih.gov/pubmed/34414020
http://dx.doi.org/10.7717/peerj.11591
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author Guo, Jianfeng
Zhu, Yapei
Yu, Lili
Li, Yuan
Guo, Jing
Cai, Jing
Liu, Lin
Wang, Zehua
author_facet Guo, Jianfeng
Zhu, Yapei
Yu, Lili
Li, Yuan
Guo, Jing
Cai, Jing
Liu, Lin
Wang, Zehua
author_sort Guo, Jianfeng
collection PubMed
description BACKGROUND: Ovarian cancer is the most common gynecological malignancy and is difficult to manage due to the emergence of resistance to various chemotherapeutic drugs. New efforts are urgently awaited. Aspirin, which is traditionally considered a nonsteroidal anti-inflammatory drug (NSAID), has been reported to exert potential chemopreventive effects. Therefore, we aimed to investigate the anticancer effect and explore the underlying molecular mechanisms of aspirin on epithelial ovarian cancer (EOC) cells. METHODS: We conducted wound healing, transwell migration, EdU cell proliferation, colony formation and apoptosis detection assays to observe the effects of aspirin on the migration, proliferation and apoptosis of EOC cells (A2870, Caov-3, and SK-OV-3). EOC cells were treated with a combination of aspirin and cisplatin (CDDP) to observe the effect of aspirin on enhancing CDDP sensitivity. Orthotopic xenograft models of ovarian cancer established with A2780-Luciferase-GFP cells were applied to compare tumor growth inhibition in the control, CDDP and CDDP plus aspirin groups through in vivo imaging, which can be used to continuously monitor tumor growth. The expression and acetylation levels of p53 in EOC cells treated with aspirin were determined using western blotting, and p53 acetylation levels were examined in tumors harvested from the transplanted mice. Quantitative real-time PCR was used to assess the mRNA expression of p53 target genes. RESULTS: Aspirin inhibited migration and proliferation and induced apoptosis in EOC cell lines in a concentration-dependent manner. In vitro, aspirin enhanced the sensitivity of EOC cells to CDDP by increasing its inhibitory effect on proliferation and its effect on inducing apoptosis. In vivo, the differences in the tumor growth inhibition rates among the different CDDP experimental groups were statistically significant (p < 0.05). Aspirin did not affect p53 protein expression but increased the p53 acetylation level in a concentration-dependent manner. In addition, the mRNA levels of CDKN1A, BAX, FOXF1, PUMA, and RRAD in EOC cells were significantly increased by the aspirin treatment. CONCLUSIONS: Aspirin inhibits tumor progression and enhances the CDDP sensitivity of EOC cells. These antitumor effects of aspirin might be mediated by p53 acetylation and subsequent activation of p53 target genes.
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spelling pubmed-83409042021-08-18 Aspirin inhibits tumor progression and enhances cisplatin sensitivity in epithelial ovarian cancer Guo, Jianfeng Zhu, Yapei Yu, Lili Li, Yuan Guo, Jing Cai, Jing Liu, Lin Wang, Zehua PeerJ Biochemistry BACKGROUND: Ovarian cancer is the most common gynecological malignancy and is difficult to manage due to the emergence of resistance to various chemotherapeutic drugs. New efforts are urgently awaited. Aspirin, which is traditionally considered a nonsteroidal anti-inflammatory drug (NSAID), has been reported to exert potential chemopreventive effects. Therefore, we aimed to investigate the anticancer effect and explore the underlying molecular mechanisms of aspirin on epithelial ovarian cancer (EOC) cells. METHODS: We conducted wound healing, transwell migration, EdU cell proliferation, colony formation and apoptosis detection assays to observe the effects of aspirin on the migration, proliferation and apoptosis of EOC cells (A2870, Caov-3, and SK-OV-3). EOC cells were treated with a combination of aspirin and cisplatin (CDDP) to observe the effect of aspirin on enhancing CDDP sensitivity. Orthotopic xenograft models of ovarian cancer established with A2780-Luciferase-GFP cells were applied to compare tumor growth inhibition in the control, CDDP and CDDP plus aspirin groups through in vivo imaging, which can be used to continuously monitor tumor growth. The expression and acetylation levels of p53 in EOC cells treated with aspirin were determined using western blotting, and p53 acetylation levels were examined in tumors harvested from the transplanted mice. Quantitative real-time PCR was used to assess the mRNA expression of p53 target genes. RESULTS: Aspirin inhibited migration and proliferation and induced apoptosis in EOC cell lines in a concentration-dependent manner. In vitro, aspirin enhanced the sensitivity of EOC cells to CDDP by increasing its inhibitory effect on proliferation and its effect on inducing apoptosis. In vivo, the differences in the tumor growth inhibition rates among the different CDDP experimental groups were statistically significant (p < 0.05). Aspirin did not affect p53 protein expression but increased the p53 acetylation level in a concentration-dependent manner. In addition, the mRNA levels of CDKN1A, BAX, FOXF1, PUMA, and RRAD in EOC cells were significantly increased by the aspirin treatment. CONCLUSIONS: Aspirin inhibits tumor progression and enhances the CDDP sensitivity of EOC cells. These antitumor effects of aspirin might be mediated by p53 acetylation and subsequent activation of p53 target genes. PeerJ Inc. 2021-08-02 /pmc/articles/PMC8340904/ /pubmed/34414020 http://dx.doi.org/10.7717/peerj.11591 Text en ©2021 Guo et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Biochemistry
Guo, Jianfeng
Zhu, Yapei
Yu, Lili
Li, Yuan
Guo, Jing
Cai, Jing
Liu, Lin
Wang, Zehua
Aspirin inhibits tumor progression and enhances cisplatin sensitivity in epithelial ovarian cancer
title Aspirin inhibits tumor progression and enhances cisplatin sensitivity in epithelial ovarian cancer
title_full Aspirin inhibits tumor progression and enhances cisplatin sensitivity in epithelial ovarian cancer
title_fullStr Aspirin inhibits tumor progression and enhances cisplatin sensitivity in epithelial ovarian cancer
title_full_unstemmed Aspirin inhibits tumor progression and enhances cisplatin sensitivity in epithelial ovarian cancer
title_short Aspirin inhibits tumor progression and enhances cisplatin sensitivity in epithelial ovarian cancer
title_sort aspirin inhibits tumor progression and enhances cisplatin sensitivity in epithelial ovarian cancer
topic Biochemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340904/
https://www.ncbi.nlm.nih.gov/pubmed/34414020
http://dx.doi.org/10.7717/peerj.11591
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