Journal
CELL BIOLOGY INTERNATIONAL
Volume 43, Issue 2, Pages 98-107Publisher
WILEY
DOI: 10.1002/cbin.11026
Keywords
Cbl-b; EGFR-TKI; NF-kappa B; NSCLC; proliferation
Categories
Funding
- National Natural Science Foundation of China [81472193, 81372546, 81270036]
- general project of liaoning province department of education [L2014296]
- Program for Liaoning Excellent Talents in University [LR2014023]
- Key Research and Development Program of Shenyang [17-230-9-01]
Ask authors/readers for more resources
Although epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) could greatly improve the prognosis of NSCLC patients harboring activating EGFR mutations, drug resistance still remains a major obstacle to successful treatment. Our previous study found that the EGFR-TKI icotinib could upregulate the expression of Casitas-B-lineage lymphoma protein-B (Cbl-b), an E3 ubiquitin ligase. In the present study, we aimed to clarify the potential role of Cbl-b in the resistance to icotinib, and the underlying mechanisms using EGFR-mutant cell lines. We found that icotinib inhibited the proliferation of mutant-EGFR NSCLC cells (PC9 and HCC827), and upregulated the expression of Cbl-b at both the protein and mRNA levels. Cbl-b knockdown decreased the sensitivity of PC9 and HCC827 cells to icotinib, and partially restored icotinib-inhibited AKT activation in PC9 cells. On the contrary, Cbl-b overexpression could partly reverse the drug resistance in PC9 icotinib-resistant cells (PC9/IcoR). Moreover, overexpressing p65, the main member of transcription factor NF-kappa B family, reversed the icotinib-mediated upregulation of Cbl-b. Collectively, these data suggest that icotinib could upregulate Cbl-b mediated by NF-kappa B inhibition, and Cbl-b contribute to the icotinib sensitivity in EGFR-mutant NSCLC cells. This study highlights that low expression of Cbl-b might be the key obstacles in the efficacy of icotinib therapy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available