Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression

被引:16
作者
Liu, Kun [1 ,2 ]
Pu, Jun [3 ]
Nie, Zhi [1 ,2 ]
Shi, Yulin [1 ,2 ]
Jiang, Liping [1 ]
Wu, Qisheng [1 ]
Chen, Yongbin [1 ,2 ,4 ]
Yang, Cuiping [1 ,2 ]
机构
[1] Chinese Acad Sci & Yunnan Prov, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mech, Kunming, Yunnan, Peoples R China
[2] Univ Chinese Acad Sci, Kunming Coll Life Sci, Beijing, Peoples R China
[3] Kunming Med Univ, Affiliated Hosp 2, Dept Neurosurg, Kunming, Yunnan, Peoples R China
[4] Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming, Yunnan, Peoples R China
基金
中国国家自然科学基金;
关键词
ivacaftor; glioblastoma; glioblastoma stem cell; apoptosis; stemness; GROWTH; CANCER; PROLIFERATION; TEMOZOLOMIDE; RESISTANCE; ACTIVATION; SURVIVAL; CAPACITY;
D O I
10.3389/fcell.2021.678209
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页数:9
相关论文
共 35 条
[1]   Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor [J].
Bao, Shideng ;
Wu, Qiulian ;
Sathornsumetee, Sith ;
Hao, Yueling ;
Li, Zhizhong ;
Hjelmeland, Anita B. ;
Shi, Oing ;
McLendon, Roger E. ;
Bigner, Darell D. ;
Rich, Jeremy N. .
CANCER RESEARCH, 2006, 66 (16) :7843-7848
[2]   Mesenchymal Differentiation Mediated by NF-κB Promotes Radiation Resistance in Glioblastoma [J].
Bhat, Krishna P. L. ;
Balasubramaniyan, Veerakumar ;
Vaillant, Brian ;
Ezhilarasan, Ravesanker ;
Hummelink, Karlijn ;
Hollingsworth, Faith ;
Wani, Khalida ;
Heathcock, Lindsey ;
James, Johanna D. ;
Goodman, Lindsey D. ;
Conroy, Siobhan ;
Long, Lihong ;
Lelic, Nina ;
Wang, Suzhen ;
Gumin, Joy ;
Raj, Divya ;
Kodama, Yoshinori ;
Raghunathan, Aditya ;
Olar, Adriana ;
Joshi, Kaushal ;
Pelloski, Christopher E. ;
Heimberger, Amy ;
Kim, Se Hoon ;
Cahill, Daniel P. ;
Rao, Ganesh ;
Den Dunnen, Wilfred F. A. ;
Boddeke, Hendrikus W. G. M. ;
Phillips, Heidi S. ;
Nakano, Ichiro ;
Lang, Frederick F. ;
Colman, Howard ;
Sulman, Erik P. ;
Aldape, Kenneth .
CANCER CELL, 2013, 24 (03) :331-346
[3]   A restricted cell population propagates glioblastoma growth after chemotherapy [J].
Chen, Jian ;
Li, Yanjiao ;
Yu, Tzong-Shiue ;
McKay, Renee M. ;
Burns, Dennis K. ;
Kernie, Steven G. ;
Parada, Luis F. .
NATURE, 2012, 488 (7412) :522-+
[4]   Cancer stem cells and glioma [J].
Das, Sunit ;
Srikanth, Maya ;
Kessler, John A. .
NATURE CLINICAL PRACTICE NEUROLOGY, 2008, 4 (08) :427-435
[5]   Inhibition of Dopamine Receptor D4 Impedes Autophagic Flux, Proliferation, and Survival of Glioblastoma Stem Cells [J].
Dolma, Sonam ;
Selvadurai, Hayden J. ;
Lan, Xiaoyang ;
Lee, Lilian ;
Kushida, Michelle ;
Voisin, Veronique ;
Whetstone, Heather ;
So, Milly ;
Aviv, Tzvi ;
Park, Nicole ;
Zhu, Xueming ;
Xu, ChangJiang ;
Head, Renee ;
Rowland, Katherine J. ;
Bernstein, Mark ;
Clarke, Ian D. ;
Bader, Gary ;
Harrington, Lea ;
Brumell, John H. ;
Tyers, Mike ;
Dirks, Peter B. .
CANCER CELL, 2016, 29 (06) :859-873
[6]   Temozolomide Treatment Induces HMGB1 to Promote the Formation of Glioma Stem Cells via the TLR2/NEAT1/Wnt Pathway in Glioblastoma [J].
Gao, Xiang-Yu ;
Zang, Jian ;
Zheng, Min-Hua ;
Zhang, Yu-Fei ;
Yue, Kang-Yi ;
Cao, Xiu-Li ;
Cao, Yuan ;
Li, Xin-Xin ;
Han, Hua ;
Jiang, Xiao-Fan ;
Liang, Liang .
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2021, 9
[7]   Impairment of Glioma Stem Cell Survival and Growth by a Novel Inhibitor for Survivin-Ran Protein Complex [J].
Guvenc, Hacer ;
Pavlyukov, Marat S. ;
Joshi, Kaushal ;
Kurt, Habibe ;
Banasavadi-Siddegowda, Yeshavanth K. ;
Mao, Ping ;
Hong, Christopher ;
Yamada, Ryosuke ;
Kwon, Chang-Hyuk ;
Bhasin, Deepak ;
Chettiar, Somsundaram ;
Kitange, Gaspar ;
Park, In-Hee ;
Sarkaria, Jann N. ;
Li, Chenglong ;
Shakhparonov, Mihail I. ;
Nakano, Ichiro .
CLINICAL CANCER RESEARCH, 2013, 19 (03) :631-642
[8]   CFTR Modulator Therapy Enhances Peripheral Blood Monocyte Contributions to Immune Responses in People With Cystic Fibrosis [J].
Hisert, Katherine B. ;
Birkland, Timothy P. ;
Schoenfelt, Kelly Q. ;
Long, Matthew E. ;
Grogan, Brenda ;
Carter, Suzanne ;
Liles, W. Conrad ;
McKone, Edward F. ;
Becker, Lev ;
Manicone, Anne M. ;
Gharib, Sina A. .
FRONTIERS IN PHARMACOLOGY, 2020, 11
[9]   Ivacaftor decreases monocyte sensitivity to interferon-γ in people with cystic fibrosis [J].
Hisert, Katherine B. ;
Birkland, Timothy P. ;
Schoenfelt, Kelly Q. ;
Long, Matthew E. ;
Grogan, Brenda ;
Carter, Suzanne ;
Liles, W. Conrad ;
McKone, Edward F. ;
Becker, Lev ;
Manicone, Anne M. .
ERJ OPEN RESEARCH, 2020, 6 (02)
[10]   Elexacaftor/Ivacaftor/Tezacaftor: First Approval [J].
Hoy, Sheridan M. .
DRUGS, 2019, 79 (18) :2001-2007