Discovery of a novel EGFR ligand DPBA that degrades EGFR and suppresses EGFR-positive NSCLC growth

摘要

DPBA specifically reduces EGFR protein level and demonstrates potent anticancer effect towards NSCLC cells lines by suppressing EGFR protein level and the downstream pro-survival pathways. a EGFR degraders screening. b Chemical structure of DPBA. c DPBA showed potent anticancer effect towards EGFR-positive cancers. EGFR protein levels of A431, A549, H1975, H1650, H522, MDA-MB-468, MDA-MB-231, MDA-MB-435, MCF-7, HepG2/ADM, HepG2, HT-29, HCT116, and SW620 were measured by Western blot. All cell lines were treated with DPBA (5 μM) for 48 h. Cell viability was detected by the MTT assay. **P < 0.01, ***P < 0.001 vs. the control (DMSO) group, n = 3. d Correlation between viability and EGFR mRNA or protein level in aforementioned cell lines. e A549, H1299, H1650, and H1975 were treated with indicated concentrations of DPBA, gefitinib, afatinib, or AZD9291 for 24 h. Cell viability was measured by the MTT assay. f Cell colonies of A549, H1299, H1650, and H1975 treated with DPBA (4, 6, or 8 μM) were counted with ImagePro Plus. **P < 0.01, ***P < 0.001 vs. 0 μM, n = 3. g DPBA suppressed EGFR pro-survival pathway by reducing EGFR protein level. A549, H1975, and H1650 were treated with DPBA (6 μM) for the indicated times. Activation of EGFR pathway and cleavage of PARP were measured by Western blot