Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression

Kun Liu; Kun Liu; Jun Pu; Zhi Nie; Zhi Nie; Yulin Shi; Yulin Shi; Liping Jiang; Qisheng Wu; Yongbin Chen; Yongbin Chen; Yongbin Chen; Cuiping Yang; Cuiping Yang

doi:10.3389/fcell.2021.678209

Frontiers in Cell and Developmental Biology (May 2021)

Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression

Kun Liu,
Kun Liu,
Jun Pu,
Zhi Nie,
Zhi Nie,
Yulin Shi,
Yulin Shi,
Liping Jiang,
Qisheng Wu,
Yongbin Chen,
Yongbin Chen,
Yongbin Chen,
Cuiping Yang,
Cuiping Yang

Affiliations

Kun Liu: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, China
Kun Liu: Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China
Jun Pu: Department of Neurosurgery, The Second Affiliated Hospital, Kunming Medical University, Kunming, China
Zhi Nie: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, China
Zhi Nie: Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China
Yulin Shi: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, China
Yulin Shi: Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China
Liping Jiang: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, China
Qisheng Wu: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, China
Yongbin Chen: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, China
Yongbin Chen: Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China
Yongbin Chen: Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China
Cuiping Yang: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, China
Cuiping Yang: Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China

DOI: https://doi.org/10.3389/fcell.2021.678209
Journal volume & issue: Vol. 9

Abstract

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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.

Published in Frontiers in Cell and Developmental Biology

ISSN: 2296-634X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: https://www.frontiersin.org/journals/cell-and-developmental-biology

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