Research Paper Volume 13, Issue 5 pp 6890—6903

MET inhibitor, capmatinib overcomes osimertinib resistance via suppression of MET/Akt/snail signaling in non-small cell lung cancer and decreased generation of cancer-associated fibroblasts

Capmatinib treatment overcomes osimertinib resistance. (A) Cell viability assay showed that capmatinib treatment (0.5μM, 24h) followed by osimertinib promoted osimertinib sensitivity in both H1975+CAF and OR cells. The combined treatment regimen: capmatinib (0.5μM, 24h) followed by osimertinib (0.25μM, 48h for H1975+CAF and 0.5μM 48h for HCC827+CAF, respectively, significantly reduced the ability of colony formation (B) migration (C) and tumor sphere generation (D). (E) Western blot analysis revealed that the sequential capmatinib and osimertinib treated H1975+CAF and OR cells showed a markedly reduced phosphorylation of MET, Akt, EGFR and expression level of vimentin (Vim) and Snail than the untreated counterparts. Lane +, treatment group; lane -, untreated group. **P

Figure 3. Capmatinib treatment overcomes osimertinib resistance. (A) Cell viability assay showed that capmatinib treatment (0.5μM, 24h) followed by osimertinib promoted osimertinib sensitivity in both H1975+CAF and OR cells. The combined treatment regimen: capmatinib (0.5μM, 24h) followed by osimertinib (0.25μM, 48h for H1975+CAF and 0.5μM 48h for HCC827+CAF, respectively, significantly reduced the ability of colony formation (B) migration (C) and tumor sphere generation (D). (E) Western blot analysis revealed that the sequential capmatinib and osimertinib treated H1975+CAF and OR cells showed a markedly reduced phosphorylation of MET, Akt, EGFR and expression level of vimentin (Vim) and Snail than the untreated counterparts. Lane +, treatment group; lane -, untreated group. **P<0.01; ***P<0.001.