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HMGB1 induces radioresistance through PI3K/AKT/ATM pathway in esophageal squamous cell carcinoma
BACKGROUND: To explore the effect of HMGB1 on the radio-sensitivity of esophageal cancer cells through regulating the PI3K/Akt/ATM pathway. METHODS AND RESULTS: We observed the expression of HMGB1 and p-ATM in biopsies of esophageal cancer patients with immunohistochemical staining. Western blot and...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9712304/ https://www.ncbi.nlm.nih.gov/pubmed/36260180 http://dx.doi.org/10.1007/s11033-022-07989-8 |
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author | Zhang, Xueyuan Zou, Naiyi Deng, Wenzhao Song, Chunyang Yan, Ke Shen, Wenbin Zhu, Shuchai |
author_facet | Zhang, Xueyuan Zou, Naiyi Deng, Wenzhao Song, Chunyang Yan, Ke Shen, Wenbin Zhu, Shuchai |
author_sort | Zhang, Xueyuan |
collection | PubMed |
description | BACKGROUND: To explore the effect of HMGB1 on the radio-sensitivity of esophageal cancer cells through regulating the PI3K/Akt/ATM pathway. METHODS AND RESULTS: We observed the expression of HMGB1 and p-ATM in biopsies of esophageal cancer patients with immunohistochemical staining. Western blot and RT-qPCR were applied to detect the protein and RNA related to PI3K/Akt/ATM pathway, respectively. In addition, we inhibited the PI3K/Akt pathway with ly294002 and activated it with IGF1, then we explored the invasion, proliferation ability, and apoptosis of esophageal cancer cells in vitro by transwell, CCK8 assay, and flow cytometry respectively. In vivo, xenograft tumor model was established in nude mice to study the effect of HMGB1 on radioresistance via PI3K/AKT/ATM Signaling Pathway. The survival rate in patients with single positive/double negative expression of HMGB1 and p-ATM was significantly higher than in those with both positive expression of HMGB1 and p-ATM, the depletion of HMGB1 combined with ly294002 significantly inhibited cell proliferation and invasion ability, meanwhile, the addition of IGF1 reversed it. Meanwhile, depletion of HMGB1 and ly294002 promoted apoptosis and arrested the cancer cells in G0/G1 cell cycle with the decreased expression of Cyclin D1 and CDK4 and improved P16. We further validated these results in vivo, the application of HMGB1 silencing promoted apoptosis of xenograft tumors after radiation, especially combined with pathway inhibitor ly294002. CONCLUSIONS: Esophageal cancer patients with high expression of HMGB1 and p-ATM have a poor prognosis after chemo-radiotherapy. Down-regulation of HMGB1 may promote the radio-sensitivity of esophageal cancer cells through regulating PI3K/Akt/ATM pathway. |
format | Online Article Text |
id | pubmed-9712304 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-97123042022-12-02 HMGB1 induces radioresistance through PI3K/AKT/ATM pathway in esophageal squamous cell carcinoma Zhang, Xueyuan Zou, Naiyi Deng, Wenzhao Song, Chunyang Yan, Ke Shen, Wenbin Zhu, Shuchai Mol Biol Rep Original Article BACKGROUND: To explore the effect of HMGB1 on the radio-sensitivity of esophageal cancer cells through regulating the PI3K/Akt/ATM pathway. METHODS AND RESULTS: We observed the expression of HMGB1 and p-ATM in biopsies of esophageal cancer patients with immunohistochemical staining. Western blot and RT-qPCR were applied to detect the protein and RNA related to PI3K/Akt/ATM pathway, respectively. In addition, we inhibited the PI3K/Akt pathway with ly294002 and activated it with IGF1, then we explored the invasion, proliferation ability, and apoptosis of esophageal cancer cells in vitro by transwell, CCK8 assay, and flow cytometry respectively. In vivo, xenograft tumor model was established in nude mice to study the effect of HMGB1 on radioresistance via PI3K/AKT/ATM Signaling Pathway. The survival rate in patients with single positive/double negative expression of HMGB1 and p-ATM was significantly higher than in those with both positive expression of HMGB1 and p-ATM, the depletion of HMGB1 combined with ly294002 significantly inhibited cell proliferation and invasion ability, meanwhile, the addition of IGF1 reversed it. Meanwhile, depletion of HMGB1 and ly294002 promoted apoptosis and arrested the cancer cells in G0/G1 cell cycle with the decreased expression of Cyclin D1 and CDK4 and improved P16. We further validated these results in vivo, the application of HMGB1 silencing promoted apoptosis of xenograft tumors after radiation, especially combined with pathway inhibitor ly294002. CONCLUSIONS: Esophageal cancer patients with high expression of HMGB1 and p-ATM have a poor prognosis after chemo-radiotherapy. Down-regulation of HMGB1 may promote the radio-sensitivity of esophageal cancer cells through regulating PI3K/Akt/ATM pathway. Springer Netherlands 2022-10-19 2022 /pmc/articles/PMC9712304/ /pubmed/36260180 http://dx.doi.org/10.1007/s11033-022-07989-8 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/) . |
spellingShingle | Original Article Zhang, Xueyuan Zou, Naiyi Deng, Wenzhao Song, Chunyang Yan, Ke Shen, Wenbin Zhu, Shuchai HMGB1 induces radioresistance through PI3K/AKT/ATM pathway in esophageal squamous cell carcinoma |
title | HMGB1 induces radioresistance through PI3K/AKT/ATM pathway in esophageal squamous cell carcinoma |
title_full | HMGB1 induces radioresistance through PI3K/AKT/ATM pathway in esophageal squamous cell carcinoma |
title_fullStr | HMGB1 induces radioresistance through PI3K/AKT/ATM pathway in esophageal squamous cell carcinoma |
title_full_unstemmed | HMGB1 induces radioresistance through PI3K/AKT/ATM pathway in esophageal squamous cell carcinoma |
title_short | HMGB1 induces radioresistance through PI3K/AKT/ATM pathway in esophageal squamous cell carcinoma |
title_sort | hmgb1 induces radioresistance through pi3k/akt/atm pathway in esophageal squamous cell carcinoma |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9712304/ https://www.ncbi.nlm.nih.gov/pubmed/36260180 http://dx.doi.org/10.1007/s11033-022-07989-8 |
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