Premium
A novel synthetic compound overcomes drug resistance on EGFR (T790M) and cancer stemness in human non‐small cell lung cancer
Author(s) -
Pan Pei Ying,
Chang ChienJen,
Liu KuangKai,
Chan YuChi,
Chen YanTing,
Chao JuiI
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb181
Subject(s) - t790m , gefitinib , erlotinib , lung cancer , cancer research , epidermal growth factor receptor , egfr inhibitors , medicine , cancer , drug resistance , cancer cell , oncology , biology , microbiology and biotechnology
Drug resistance has become bottleneck in cancer therapy of non‐small cell lung carcinoma (NSCLC) patients. The mutations of epidermal growth factor receptor (EGFR) on exon 19 deletion and exon 21 point mutation are respond well to the first and second generation EGFR tyrosine kinase inhibitors (EGFR‐TKIs) such as Gefitinib and Erlotinib for NSCLC therapy; however, patients acquired the T790M mutation of EGFR will induce drug resistance. In addition, cancer stemness properties are also a pivotal factor of drug resistance in NSCLC. Accordingly, development of novel compounds for overcoming drug resistance of NSCLC is still desired. In this study, we show a novel synthetic compound derived from 5,8‐quinolinedione that has potential in overcoming drug resistance of EGFR (T790M) and cancerous stemness in NSCLC. This new compound can induce cell death and apoptosis in drug‐resistant H1975 cells, which contained EGFR (T790M). This compound inhibited Survivin protein expression and conversely increased the active caspase 3 and cleaved PARP for apoptosis induction. In addition, this compound also decreased the cell viability in drug resistance NSCLC cells, which were separated from pleural effusion of NSCLC. Moreover, it can inhibit the stemness protein expression of Oct4 in lung cancer cells. Taken together, we develop a novel compound, which further investigate for overcoming drug resistance and cancer therapy in NSCLC.