Fig. 7: TWIST1 inhibition sensitizes to MET TKIs and overcomes MET TKI resistance in MET altered NSCLC. | Oncogene

Fig. 7: TWIST1 inhibition sensitizes to MET TKIs and overcomes MET TKI resistance in MET altered NSCLC.

From: TWIST1 is a critical downstream target of the HGF/MET pathway and is required for MET driven acquired resistance in oncogene driven lung cancer

Fig. 7

A-F Cell viability assay demonstrating that genetic and pharmacological inhibition of Twist1 with shRNA and harmine overcomes resistance to tepotinib and crizotinib in H1437 (A, D), H596 (B, E) and H1648 (C, F) cell lines respectively. G Representative cell viability assay demonstrating that in MET amplified H1993 cells harmine overcomes HGF-mediated resistance to MET targeted therapy. Cells were co-treated with the indicated doses of harmine, HGF (50 ng/ml), crizotinib (100 nM) for 72 h, and then harvested for MTS analysis. Data represent mean ± SD (n = 4 technical replicates). *P < 0.05, **P < 0.01, ***P < 0.001,**** P < 0.0001, two-way ANOVA. Western blot demonstrating induction of p27 after Twist1 inhibition with shRNAs followed by capmatinib treatment in H596 (H) and I H1648 cell lines respectively. Encircled in red boxes are the panel of p27 expression which has maximum fold change (Scr vs shTWIST1-2).

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