P2.13-34 Long Intergenic Non-Coding RNA 00665 Induces Acquired Resistance to Gefitinib in Non-Small-Cell Lung Cancer

Abstract

Gefitinib, a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR-TKI), has been used as the first choice of treatment for advanced non-small cell lung cancer (NSCLC). However, during the course of treatment cancer cells often develop resistance to gefitinib without fully understood mechanisms. In recent years, numerous studies have shown that long non-coding RNAs (lncRNAs) play vital roles in modulating various biological processes, such as cell apoptosis, proliferation, migration, and invasion. Nevertheless cancer drug resistance mechanisms related to LncRNAs and their important roles in cancer development are still poorly understood. In this study, we aimed to elucidate an important role of long intergenic non-coding RNA 00665 (LINC00665) in developing resistance to gefitinib in NSCLC. Quantitative reverse transcription PCR (qRT-PCR) was performed to examine the expression levels of LINC00665 in 10 pairs of LUAD tissues from patients who had never been treated with gefitinib (NG) and those who were treated with gefitinib but developed resistance (GR). The effect of LINC00665 on proliferation and apoptosis in gefitinib-resistant cells was evaluated by CCK8, colony formation, flow-cytometric analysis and in vivo tumor formation assays. Western-blot and immunohistochemistry were used to evaluate the expression of EGFR and its downstream event. LINC00665 expression levels were significantly increased in NSCLC patients who developed acquired resistance to gefitinib compared to the NG group.Furthermore, LINC00665 inhibition reversed gefitinib sensitivity both in vitro and in vivo by suppressing cell growth and induced cell apoptosis. Importantly, knockdown of LINC00665 marked decreased activation of EGFR and its downstream event Akt and ERK1/2. Taken together,our study demonstrates that LINC00665 may be a potential biomarker of response to gefitinib as well as a novel therapeutic target for future treatment of NSCLC.