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Journal of Cancer Prevention

Original Article

Journal of Cancer Prevention 2015; 20(1): 57-63

Published online March 30, 2015

© Korean Society of Cancer Prevention

Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Growth of Gefitinib-resistant Non-small Cell Lung Cancer Cells by Inducing Apoptosis

Chul-Ho Jeong

College of Pharmacy, Keimyung University, Daegu, Korea

Correspondence to :
Chul-Ho Jeong, College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Dalseo-gu, Daegu 704-919 Korea, Tel: +82-53-580-6638, Fax: +82-53-580-5164, E-mail:, ORCID: Chul-Ho Jeong,

Received: February 6, 2015; Revised: February 26, 2015; Accepted: February 26, 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.



Therapeutic approach by treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) like gefitinib or erlotinib to non-small cell lung cancer (NSCLC) patients has been limited due to emergence of acquired drug resistance. Our study was aimed to investigate whether the inhibition of ubiquitin-specific peptidase 8 (USP8) could be an alternative strategy capable of overcoming acquired resistance to EGFR-TKIs for treatment of NSCLCs.


The anticancer effect of USP8 inhibitor was determined by testing anchorage-dependent or independent growth of gefitinib-sensitive or resistant NSCLCs. The immunoprecipitation and western blotting were conducted to check molecular interaction and signaling pathway followed by USP8 inhibition.


Inhibition of USP8 induced overall degradation of oncogenic receptor tyrosine kinases including EGFR and Met, leading to a suppression of anchorage-dependent or independent cell growth of gefitinib-sensitive or resistant NSCLCs. Also, treatment with the USP8 inhibitor markedly induced apoptosis in HCC827GR cells. Notably, treatment with the USP8 inhibitor was more effective in suppressing cell growth and inducing apoptosis in gefitinib-resistant HCC827GR cells than that of gefitinib-sensitive HCC827 cells.


Inhibition of USP8 could be an effective strategy for overcoming gefitinib resistance in NSCLCs.

Keywords: USP8, Non-small cell lung cancer, Gefitinib, Apoptosis, Resistance

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