Figure 7: The MET inhibitor crizotinib restores rociletinib sensitivity and downstream pathway suppression.

(a) Erlotinib resistant (ER) and rociletinib-resistant (RR) tumour-derived cell lines respond to rociletinib and rociletinib combined with crizotinib, respectively. Cell viability was evaluated in ER and RR tumour-derived cell lines after treatment with erlotinib, rociletinib and/or crizotinib for 72 h. Experiments were performed in triplicate, repeated three times and data are plotted as mean percentage viability±s.d. relative to control. The data summary table reflects these 3 experiments and the values reported are the mean 50% growth inhibition±s.d. (nM). (b) Western blot analysis of PC-9 parental, erlotinib resistant, and rociletinib-resistant cell lines following 1-h incubations with the compounds indicated. (c) PC-9 parental and rociletinib-resistant tumour-derived cell lines were infected with a lentivirus expressing MET-specific or scrambled control shRNAs. Cell viability was evaluated after treatment with rociletinib and/or crizotinib for 72 h. Data are plotted as mean percentage viability±s.d. relative to control. (d) Western blot analysis of PC-9 parental and rociletinib-resistant (RR) cell lines transfected with control or MET shRNA and treated with rociletinib.