Inhibition of NF-κB Signaling Reduces the Stemness Characteristics of Lung Cancer Stem Cells

Frontiers in Oncology

卷:8

Zubaidah Zakaria¹  Badrul Hisham Yahaya²  Narazah Mohd Yusoff²  Norashikin Zakaria²  Darius Widera³ 

[1] Cancer Research Centre, Institute for Medical Research (IMR), Kuala Lumpur, Malaysia;

[2] Regenerative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Penang, Malaysia;

[3] Stem Cell Biology and Regenerative Medicine, School of Pharmacy, University of Reading, Reading, United Kingdom;

关键词: NF-κB signaling;    lung cancer;    cancer stem cells;    cancer migration;    self-renewal;   

DOI  :  10.3389/fonc.2018.00166

来源: DOAJ

【 摘 要 】

Cancer stem cells (CSCs) are a subpopulation of cancer cells that play a pivotal role in tumor development, invasion, metastasis, and recurrence. We and others have reported significant involvement of the NF-κB pathway in regulating CSCs of non-small cell lung cancer (NSCLC). In this study, we evaluated the effects of NF-κB inhibition on self-renewal, stemness, migration, and expression of genes involved in the epithelial to mesenchymal transition (EMT) and apoptosis resistance in lung CSCs. Different concentrations of the NF-κB inhibitor BMS-345541 (0.4, 4.0, and 10.0 µM), an inhibitor the NF-κB upstream kinase IKKβ, were used to treat both lung CSCs (CD166+CD44+, CD166+EpCAM+) and non-CSC NSCLC cells (CD166−CD44−, CD166−EpCAM−) in A549 and H2170 cell lines. We assessed the impact of BMS-345541 on the ability to form tumorspheres (self-renewal assay), expression of stemness genes (SOX2, OCT4, NANOG, SCA-1, and KLF4), migration, and expression of EMT and apoptosis-related genes. Inhibition of NF-κB by BMS-345541 effectively reduced the stemness, self-renewal, and migration capacity of lung CSCs. Moreover, expression of genes involved in the EMT (SNAI1 and TWIST) and apoptosis resistance (BCL-2, BAX, and BIRC5) was significantly reduced following the treatments, suggesting that NF-κB inhibition is sufficient to prevent the EMT and induce apoptosis in lung CSCs. Our findings suggest that NF-κB inhibition could reduce the capability of CSCs to maintain their population within the tumor mass, potentially decelerating cancer progression, relapse, and chemotherapy resistance.

【 授权许可】

Unknown