Premium
SP101, a novel synthetic compound displays survivin suppression, apoptosis and tumor inhibition in both the EGFR‐wild type and ‐T790M of non‐small cell lung cancer
Author(s) -
Chao JuiI
Publication year - 2019
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.2019.33.1_supplement.lb234
Subject(s) - survivin , gefitinib , t790m , lung cancer , cancer research , apoptosis , epidermal growth factor receptor , medicine , programmed cell death , cancer , cancer cell , biology , oncology , biochemistry
Gefitinib is a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR‐TKI) which is currently used therapy in non‐small cell lung cancer (NSCLC) patients; however, drug resistance of cancer patients treatment is a critical problem. Here, we show a novel synthetic compound, dodecyl‐4‐(4‐(3‐(4‐(3‐chloro‐4‐fluorophenylamino)‐7‐methoxyquinazolin‐6‐yloxy)propyl)piperazin‐1‐yl)‐4‐oxobutanoate derivative from gefitinib, which is called SP101 that attenuated drug resistance in both the EGFR‐wild type and ‐T790M of non‐small cell lung cancer. SP101 inhibited EGFR kinase activity in the gefitinib‐resistant lung cancer cells. SP101 induced cancer cell death and apoptosis in both the A549 (EGFR‐wild type) and H1975 (EGFR‐T790M) lung cancer cells. SP101 inhibited anti‐apoptotic Survivin protein levels but conversely induced active caspase 3 proteins for apoptosis induction. The ectopic expression of survivin by a survivin‐expressed vector decreased the SP101‐induced cell death. The cell death was higher after treatment with SP101 than that gefitinib in the drug‐resistant H1975 cells. SP101 inhibited tumor growth and substantially reduced survivin protein but conversely elicited active caspase 3 in the xenograft human H1975 lung tumors of nude mice. Moreover, SP101 markedly inhibited the patient‐derived xenografted patient's lung tumors in nude mice. We demonstrate a novel compound SP101 that can reduce the drug resistance of the EGFR mutation at T790M as well as the EGFR wild type in lung cancer cells. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .