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Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression
Glioblastoma (GBM) is the most common and malignant primary brain tumor. Glioblastoma stem cells (GSCs) not only initiate and sustain uncontrolled cell proliferation but also resistant to conventional clinical therapies including temozolomide (TMZ) dependent chemotherapy and radiotherapy, implying t...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147559/ https://www.ncbi.nlm.nih.gov/pubmed/34046412 http://dx.doi.org/10.3389/fcell.2021.678209 |
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author | Liu, Kun Pu, Jun Nie, Zhi Shi, Yulin Jiang, Liping Wu, Qisheng Chen, Yongbin Yang, Cuiping |
author_facet | Liu, Kun Pu, Jun Nie, Zhi Shi, Yulin Jiang, Liping Wu, Qisheng Chen, Yongbin Yang, Cuiping |
author_sort | Liu, Kun |
collection | PubMed |
description | Glioblastoma (GBM) is the most common and malignant primary brain tumor. Glioblastoma stem cells (GSCs) not only initiate and sustain uncontrolled cell proliferation but also resistant to conventional clinical therapies including temozolomide (TMZ) dependent chemotherapy and radiotherapy, implying that there is an urgent need to identify new therapeutic strategies especially specific targeting GSCs. Here, we provide evidence showing that ivacaftor commonly applied in cystic fibrosis therapy acts as a potent inhibitor for GSCs maintenance. We found that ivacaftor promotes cellular apoptosis in vitro and represses patient-derived xenograft (PDX) tumor growth in vivo. In addition, we demonstrate that ivacaftor decreases stemness marker gene expressions of GSCs, including CD133, CD44, and Sox2. In summary, our findings reveal that ivacaftor inhibits glioblastoma progression via specifically eliminating GSCs, which opens a new avenue for GBM clinical therapy in the future. |
format | Online Article Text |
id | pubmed-8147559 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81475592021-05-26 Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression Liu, Kun Pu, Jun Nie, Zhi Shi, Yulin Jiang, Liping Wu, Qisheng Chen, Yongbin Yang, Cuiping Front Cell Dev Biol Cell and Developmental Biology Glioblastoma (GBM) is the most common and malignant primary brain tumor. Glioblastoma stem cells (GSCs) not only initiate and sustain uncontrolled cell proliferation but also resistant to conventional clinical therapies including temozolomide (TMZ) dependent chemotherapy and radiotherapy, implying that there is an urgent need to identify new therapeutic strategies especially specific targeting GSCs. Here, we provide evidence showing that ivacaftor commonly applied in cystic fibrosis therapy acts as a potent inhibitor for GSCs maintenance. We found that ivacaftor promotes cellular apoptosis in vitro and represses patient-derived xenograft (PDX) tumor growth in vivo. In addition, we demonstrate that ivacaftor decreases stemness marker gene expressions of GSCs, including CD133, CD44, and Sox2. In summary, our findings reveal that ivacaftor inhibits glioblastoma progression via specifically eliminating GSCs, which opens a new avenue for GBM clinical therapy in the future. Frontiers Media S.A. 2021-05-11 /pmc/articles/PMC8147559/ /pubmed/34046412 http://dx.doi.org/10.3389/fcell.2021.678209 Text en Copyright © 2021 Liu, Pu, Nie, Shi, Jiang, Wu, Chen and Yang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Liu, Kun Pu, Jun Nie, Zhi Shi, Yulin Jiang, Liping Wu, Qisheng Chen, Yongbin Yang, Cuiping Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression |
title | Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression |
title_full | Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression |
title_fullStr | Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression |
title_full_unstemmed | Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression |
title_short | Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression |
title_sort | ivacaftor inhibits glioblastoma stem cell maintenance and tumor progression |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147559/ https://www.ncbi.nlm.nih.gov/pubmed/34046412 http://dx.doi.org/10.3389/fcell.2021.678209 |
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