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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...

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Autores principales: Liu, Kun, Pu, Jun, Nie, Zhi, Shi, Yulin, Jiang, Liping, Wu, Qisheng, Chen, Yongbin, Yang, Cuiping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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.
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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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