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. Author manuscript; available in PMC: 2021 Mar 15.
Published in final edited form as: Cancer. 2019 Dec 10;126(6):1339–1350. doi: 10.1002/cncr.32655

Fig. 2. ERK inhibition combined with osimertinib induces the elevation of Bim levels, enhances Mcl-1 reduction (A) and enhances Bim- and Mcl-1-dependent induction of apoptosis (B-F) in osimertinib-resistant cells.

Fig. 2.

A, The indicated cell lines were treated with DMSO, 200 nM osimertinib (Osim) alone, GDC0994 (GDC) alone, VRT752271 (VRT) alone or osimertinib combined with GDC or VRT for 16 h. The proteins of interest were detected with Western blotting. B-D, Bim-deficient cell lines derived from PC-9/AR, as confirmed with Western blotting (B), together with PC-9/AR parental cells were exposed to DMSO, 100 nM Osim, 2 μM GDC or their combination for 48 h. Annexin V-positive cells were evaluated with flow cytometry (C) and protein cleavage was detected with Western blotting (D). E and F, The given cell lines were exposed to DMSO, 100 nM Osim, 4 μM GDC or their combination for 48 h. Apoptosis was evaluated by Annexin V flow cytometry (E) and by detection of PARP cleavage with Western blotting (F). The data in C and F are means ± SDs of duplicate determinations. *** P < 0.001 compared with the effect of the combination in control cells.