Ubiquitin Ligase Cbl-b Is Involved in Icotinib (BPI-2009H)-Induced Apoptosis and G1 Phase Arrest of EGFR Mutation-Positive Non-Small-Cell Lung Cancer
Joint Authors
Zhang, Ye
Hou, Kezuo
Liu, Yunpeng
Mu, Xiaodong
Qu, Xiujuan
Kang, Jian
Hu, Xuejun
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-03-19
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Epidermal growth factor receptor (EGFR) is one of the most promising targets for non-small-cell lung cancer (NSCLC).
Icotinib, a highly selective EGFR tyrosine kinase inhibitor (EGFR-TKI), has shown promising clinical efficacy and safety in patients with NSCLC.
The exact molecular mechanism of icotinib remains unclear.
In this study, we first investigated the antiproliferative effect of icotinib on NSCLC cells.
Icotinib significantly inhibited proliferation of the EGFR-mutated lung cancer HCC827 cells.
The IC50 values at 48 and 72 h were 0.67 and 0.07 μM, respectively.
Flow cytometric analysis showed that icotinib caused the G1 phase arrest and increased the rate of apoptosis in HCC827 cells.
The levels of cyclin D1 and cyclin A2 were decreased.
The apoptotic process was associated with activation of caspase-3, -8, and poly(ADP-ribose) polymerase (PARP).
Further study revealed that icotinib inhibited phosphorylation of EGFR, Akt, and extracellular signal-regulated kinase.
In addition, icotinib upregulated ubiquitin ligase Cbl-b expression.
These observations suggest that icotinib-induced upregulation of Cbl-b is responsible, at least in part, for the antitumor effect of icotinib via the inhibition of phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinase pathways in EGFR-mutated NSCLC cells.
American Psychological Association (APA)
Mu, Xiaodong& Zhang, Ye& Qu, Xiujuan& Hou, Kezuo& Kang, Jian& Hu, Xuejun…[et al.]. 2013. Ubiquitin Ligase Cbl-b Is Involved in Icotinib (BPI-2009H)-Induced Apoptosis and G1 Phase Arrest of EGFR Mutation-Positive Non-Small-Cell Lung Cancer. BioMed Research International،Vol. 2013, no. 2013, pp.1-8.
https://search.emarefa.net/detail/BIM-1030848
Modern Language Association (MLA)
Mu, Xiaodong…[et al.]. Ubiquitin Ligase Cbl-b Is Involved in Icotinib (BPI-2009H)-Induced Apoptosis and G1 Phase Arrest of EGFR Mutation-Positive Non-Small-Cell Lung Cancer. BioMed Research International No. 2013 (2013), pp.1-8.
https://search.emarefa.net/detail/BIM-1030848
American Medical Association (AMA)
Mu, Xiaodong& Zhang, Ye& Qu, Xiujuan& Hou, Kezuo& Kang, Jian& Hu, Xuejun…[et al.]. Ubiquitin Ligase Cbl-b Is Involved in Icotinib (BPI-2009H)-Induced Apoptosis and G1 Phase Arrest of EGFR Mutation-Positive Non-Small-Cell Lung Cancer. BioMed Research International. 2013. Vol. 2013, no. 2013, pp.1-8.
https://search.emarefa.net/detail/BIM-1030848
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1030848