Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression.
Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression.
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DOI：
10.3389/fcell.2021.678209
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发表时间：
2021
影响因子：
5.5
通讯作者：
Yang C
中科院分区：
文献类型：
--
作者：
Liu K;Pu J;Nie Z;Shi Y;Jiang L;Wu Q;Chen Y;Yang C
胶质母细胞瘤（GBM）是最常见的恶性原发性脑肿瘤。胶质母细胞瘤干细胞（GSC）不仅启动和维持不受控制的细胞增殖，而且对包括替莫唑胺（TMZ）依赖性化疗和放疗在内的常规临床治疗具有抗性，这意味着迫切需要确定新的治疗策略，特别是特异性靶向GSC。在这里，我们提供的证据表明，常用于囊性纤维化治疗的依伐卡托作为一种有效的抑制剂，用于维持GSC。我们发现ivacaftor在体外促进细胞凋亡，并在体内抑制患者来源的异种移植（PDX）肿瘤生长。此外，我们证明了ivacaftor降低了GSC的干性标志物基因表达，包括CD133，CD44和Sox 2。总之，我们的研究结果表明，ivacaftor通过特异性消除GSC来抑制胶质母细胞瘤的进展，这为未来GBM的临床治疗开辟了新的途径。
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.