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p53-dependent apoptosis is essential for the antitumor effect of paclitaxel response to DNA damage in papillary thyroid carcinoma
A functional p53 protein plays an important role in killing tumor cells. Previous studies showed that chemotherapeutic drug, paclitaxel (PTX), showed anti-tumor activity through inducing G2/M arrest and apoptosis by targeting microtubules in tumor cells. However, PTX was not sensitive to p53-inactiv...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364467/ https://www.ncbi.nlm.nih.gov/pubmed/34400889 http://dx.doi.org/10.7150/ijms.61944 |
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author | Wu, Wenshuang Wei, Tao Li, ZhiHui Zhu, Jingqiang |
author_facet | Wu, Wenshuang Wei, Tao Li, ZhiHui Zhu, Jingqiang |
author_sort | Wu, Wenshuang |
collection | PubMed |
description | A functional p53 protein plays an important role in killing tumor cells. Previous studies showed that chemotherapeutic drug, paclitaxel (PTX), showed anti-tumor activity through inducing G2/M arrest and apoptosis by targeting microtubules in tumor cells. However, PTX was not sensitive to p53-inactivated papillary thyroid carcinoma (PTC) cells by inducing G2/M arrest only. Recombinant adenovirus-p53 (rAd-p53) was used to increase the level of p53, which significantly increased the sensitivity of PTC cells to PTX by inducing S arrest, G2/M arrest and apoptosis. To discuss the anti-tumor mechanism of rAd-p53 + PTX and found p53 activation was necessary for anti-tumor effect of PTX in PTC cells. There was high level of p53 in rAd-p53-treated PTC cells. rAd-p53 + PTX increased the level of p21, p-ATM and γ-H2AX and decreased the level of Cyclin D1/E1, suggesting p53 activated p21 which negatively regulated cyclins to induce S arrest response to DNA damage in PTC cells. rAd-p53 + PTX increased the levels of cleaved-PARP-1, cleaved -Caspase 3, and BAX and decreased the level of BCL-XL, suggesting p53 regulates the expression of BAX/BCL-XL to mediate DNA damage-induced apoptosis in PTC cells. Furthermore, rAd-p53 + PTX showed significant tumor inhibition in TPC-1 xenograft model, with an inhibitory rate of 79.39%. TUNEL assay showed rAd-p53 + PTX induced notable apoptosis in tumor tissues. rAd-p53 showed good sensitization of PTX in vitro and in vivo through inducing DNA damage induced-apoptosis indicated p53-dependent apoptosis was essential for the antitumor effect of PTX in PTC. |
format | Online Article Text |
id | pubmed-8364467 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-83644672021-08-15 p53-dependent apoptosis is essential for the antitumor effect of paclitaxel response to DNA damage in papillary thyroid carcinoma Wu, Wenshuang Wei, Tao Li, ZhiHui Zhu, Jingqiang Int J Med Sci Research Paper A functional p53 protein plays an important role in killing tumor cells. Previous studies showed that chemotherapeutic drug, paclitaxel (PTX), showed anti-tumor activity through inducing G2/M arrest and apoptosis by targeting microtubules in tumor cells. However, PTX was not sensitive to p53-inactivated papillary thyroid carcinoma (PTC) cells by inducing G2/M arrest only. Recombinant adenovirus-p53 (rAd-p53) was used to increase the level of p53, which significantly increased the sensitivity of PTC cells to PTX by inducing S arrest, G2/M arrest and apoptosis. To discuss the anti-tumor mechanism of rAd-p53 + PTX and found p53 activation was necessary for anti-tumor effect of PTX in PTC cells. There was high level of p53 in rAd-p53-treated PTC cells. rAd-p53 + PTX increased the level of p21, p-ATM and γ-H2AX and decreased the level of Cyclin D1/E1, suggesting p53 activated p21 which negatively regulated cyclins to induce S arrest response to DNA damage in PTC cells. rAd-p53 + PTX increased the levels of cleaved-PARP-1, cleaved -Caspase 3, and BAX and decreased the level of BCL-XL, suggesting p53 regulates the expression of BAX/BCL-XL to mediate DNA damage-induced apoptosis in PTC cells. Furthermore, rAd-p53 + PTX showed significant tumor inhibition in TPC-1 xenograft model, with an inhibitory rate of 79.39%. TUNEL assay showed rAd-p53 + PTX induced notable apoptosis in tumor tissues. rAd-p53 showed good sensitization of PTX in vitro and in vivo through inducing DNA damage induced-apoptosis indicated p53-dependent apoptosis was essential for the antitumor effect of PTX in PTC. Ivyspring International Publisher 2021-07-11 /pmc/articles/PMC8364467/ /pubmed/34400889 http://dx.doi.org/10.7150/ijms.61944 Text en © The author(s) 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/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Wu, Wenshuang Wei, Tao Li, ZhiHui Zhu, Jingqiang p53-dependent apoptosis is essential for the antitumor effect of paclitaxel response to DNA damage in papillary thyroid carcinoma |
title | p53-dependent apoptosis is essential for the antitumor effect of paclitaxel response to DNA damage in papillary thyroid carcinoma |
title_full | p53-dependent apoptosis is essential for the antitumor effect of paclitaxel response to DNA damage in papillary thyroid carcinoma |
title_fullStr | p53-dependent apoptosis is essential for the antitumor effect of paclitaxel response to DNA damage in papillary thyroid carcinoma |
title_full_unstemmed | p53-dependent apoptosis is essential for the antitumor effect of paclitaxel response to DNA damage in papillary thyroid carcinoma |
title_short | p53-dependent apoptosis is essential for the antitumor effect of paclitaxel response to DNA damage in papillary thyroid carcinoma |
title_sort | p53-dependent apoptosis is essential for the antitumor effect of paclitaxel response to dna damage in papillary thyroid carcinoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364467/ https://www.ncbi.nlm.nih.gov/pubmed/34400889 http://dx.doi.org/10.7150/ijms.61944 |
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