Integrin β1 participates in acquired resistance to gefitinib in non-small cell lung cancer
10.3724/SP.J.1008.2012.00585
- Author:
Qin-fang DENG
1
Author Information
1. Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine
- Publication Type:Journal Article
- Keywords:
Epidermal growth factor receptor;
Integrin;
Neoplasm drug resistance;
Tyrosine kinase inhibitor
- From:
Academic Journal of Second Military Medical University
2012;33(6):585-589
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the role of integrin β1 and relevant signaling pathway in acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib in non-small cell lung cancer (NSCLC). Methods Human lung adenocarcinoma cell line PC-9 and gefitinib-resistant PC-9/G cell lines were used in the present study. Western blotting analysis was used to examine the expression of integrin β1, Akt and phospho-Akt protein. The inhibitory effects of gefitinib and/or phosphoinositide 3-kinase (PI3K) inhibitor LY294002 and extracellular regulated protein kinases (ERK) inhibitor PD98059 on cellular proliferation were tested by MTT assay. Cell apoptosis was analyzed by Annexin V/PI and TUNEL method. Results Overexpression of integrin β1 was observed in PC-9/G cell line. Silencing integrin β1 by RNAi method inhibited the proliferation and promoted apoptosis of PC-9/G cells. The inhibitory effect of gefitinib against Akt phosphorylation in PC-9/G cells was weaker than that in PC-9 cells. Knockdown of integrin β1 with RNAi decreased the phosphorylation level of Akt. ERK inhibitor PD98059 failed to restore the sensitivity of PC-9/G cells to gefitinib. PI3K inhibitor LY294002 could restore the sensitivity of PC-9/G cells to gefitinib. Conclusion It is suggested that overexpressed integrin β1 can activate the downstream signaling pathways through PI3K, which may be an important mechanism for resistance to EGFR-TKIs.
