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PARP inhibitor Olaparib increases the sensitization to radiotherapy in FaDu cells

Radioresistance causes a major problem for improvement of outcomes of patients treated with radiation. Targeting for DNA repair deficient mechanisms is a hallmark of sensitization to resistance. We tested whether Olaparib, a (poly) ADP‐ribose polymerase (PARP) inhibitor, can sensitize the radioresis...

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Autores principales: Liu, Chuan, Gross, Neil, Li, Yanshi, Li, Guojun, Wang, Zhihai, Zhong, Shixun, Li, Yuncheng, Hu, Guohua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028864/
https://www.ncbi.nlm.nih.gov/pubmed/31957270
http://dx.doi.org/10.1111/jcmm.14929
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author Liu, Chuan
Gross, Neil
Li, Yanshi
Li, Guojun
Wang, Zhihai
Zhong, Shixun
Li, Yuncheng
Hu, Guohua
author_facet Liu, Chuan
Gross, Neil
Li, Yanshi
Li, Guojun
Wang, Zhihai
Zhong, Shixun
Li, Yuncheng
Hu, Guohua
author_sort Liu, Chuan
collection PubMed
description Radioresistance causes a major problem for improvement of outcomes of patients treated with radiation. Targeting for DNA repair deficient mechanisms is a hallmark of sensitization to resistance. We tested whether Olaparib, a (poly) ADP‐ribose polymerase (PARP) inhibitor, can sensitize the radioresistant FaDu cells to radiotherapy. Radioresistant FaDu cells, called FaDu‐RR cells, were used as the radioresistant hypopharyngeal cancer models. The expression of PARP1 was detected in both FaDu and FaDu‐RR cells. The role of Olaparib in radiosensitization was analysed with several assays including clonogenic cell survival, cell proliferation and cell cycle, and radioresistant xenograft. High expression of PARP1 had a significant effect on enhancing radioresistance in FaDu‐RR cells compared with FaDu cells. After treatment of Olaparib, FaDu‐RR cells showed significantly less and smaller surviving colonies, lower proliferation ability and G2/M arrest than those in the group without treatment. Moreover, Olaparib significantly reduced growth of tumours in FaDu‐RR cell xenografts treated with ionizing radiation. Olaparib can significantly inhibit PARP1 expression and consequently has significant effects on radiosensitization in FaDu‐RR cells. These results indicate that Olaparib may help individualize treatment and improve their outcomes of hypopharyngeal cancer patients treated with radiation.
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spelling pubmed-70288642020-02-19 PARP inhibitor Olaparib increases the sensitization to radiotherapy in FaDu cells Liu, Chuan Gross, Neil Li, Yanshi Li, Guojun Wang, Zhihai Zhong, Shixun Li, Yuncheng Hu, Guohua J Cell Mol Med Original Articles Radioresistance causes a major problem for improvement of outcomes of patients treated with radiation. Targeting for DNA repair deficient mechanisms is a hallmark of sensitization to resistance. We tested whether Olaparib, a (poly) ADP‐ribose polymerase (PARP) inhibitor, can sensitize the radioresistant FaDu cells to radiotherapy. Radioresistant FaDu cells, called FaDu‐RR cells, were used as the radioresistant hypopharyngeal cancer models. The expression of PARP1 was detected in both FaDu and FaDu‐RR cells. The role of Olaparib in radiosensitization was analysed with several assays including clonogenic cell survival, cell proliferation and cell cycle, and radioresistant xenograft. High expression of PARP1 had a significant effect on enhancing radioresistance in FaDu‐RR cells compared with FaDu cells. After treatment of Olaparib, FaDu‐RR cells showed significantly less and smaller surviving colonies, lower proliferation ability and G2/M arrest than those in the group without treatment. Moreover, Olaparib significantly reduced growth of tumours in FaDu‐RR cell xenografts treated with ionizing radiation. Olaparib can significantly inhibit PARP1 expression and consequently has significant effects on radiosensitization in FaDu‐RR cells. These results indicate that Olaparib may help individualize treatment and improve their outcomes of hypopharyngeal cancer patients treated with radiation. John Wiley and Sons Inc. 2020-01-19 2020-02 /pmc/articles/PMC7028864/ /pubmed/31957270 http://dx.doi.org/10.1111/jcmm.14929 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Liu, Chuan
Gross, Neil
Li, Yanshi
Li, Guojun
Wang, Zhihai
Zhong, Shixun
Li, Yuncheng
Hu, Guohua
PARP inhibitor Olaparib increases the sensitization to radiotherapy in FaDu cells
title PARP inhibitor Olaparib increases the sensitization to radiotherapy in FaDu cells
title_full PARP inhibitor Olaparib increases the sensitization to radiotherapy in FaDu cells
title_fullStr PARP inhibitor Olaparib increases the sensitization to radiotherapy in FaDu cells
title_full_unstemmed PARP inhibitor Olaparib increases the sensitization to radiotherapy in FaDu cells
title_short PARP inhibitor Olaparib increases the sensitization to radiotherapy in FaDu cells
title_sort parp inhibitor olaparib increases the sensitization to radiotherapy in fadu cells
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028864/
https://www.ncbi.nlm.nih.gov/pubmed/31957270
http://dx.doi.org/10.1111/jcmm.14929
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