Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression

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

doi:10.3389/fcell.2021.678209

Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression

Front Cell Dev Biol. 2021 May 11:9:678209. doi: 10.3389/fcell.2021.678209. eCollection 2021.

Authors

Kun Liu^{1

2}, Jun Pu³, Zhi Nie^{1

2}, Yulin Shi^{1

2}, Liping Jiang¹, Qisheng Wu¹, Yongbin Chen^{1

2

4}, Cuiping Yang^{1

2}

Affiliations

¹ Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, China.
² Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
³ Department of Neurosurgery, The Second Affiliated Hospital, Kunming Medical University, Kunming, China.
⁴ Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China.

Abstract

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.

Keywords: apoptosis; glioblastoma; glioblastoma stem cell; ivacaftor; stemness.