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

MET expression is positively correlated with osimertinib resistance in NSCLC cells. (A) MET silencing (loss of function, LF) reduced osimertinib resistance in clinical NSCLC cells (osimertinib resistant cells, OR) and overexpression of MET (gain of function, GF) increased osimertinib resistance. The insert shows the MET expression in LF and GF in the OR cells. NC, normal control (vector control). LF MET reduced colony formation (B) migration (C) and tumor sphere generation (D) in OR cells. (E) Comparative western blots of MET LF and GF OR cells. MET-silenced OR cells revealed a clear reduction in the expression of MET, phosphorylated forms of MET and Akt (p-MET and p-Akt respectively), β-catenin, and Snail while the opposite was observed in the MET overexpressing (GF) counterparts. (F) CAF co-cultured with MET LF OR cells secreted a significantly lower IL-6 into the culture medium as compared to MET GF OR cells. **P

Figure 4. MET expression is positively correlated with osimertinib resistance in NSCLC cells. (A) MET silencing (loss of function, LF) reduced osimertinib resistance in clinical NSCLC cells (osimertinib resistant cells, OR) and overexpression of MET (gain of function, GF) increased osimertinib resistance. The insert shows the MET expression in LF and GF in the OR cells. NC, normal control (vector control). LF MET reduced colony formation (B) migration (C) and tumor sphere generation (D) in OR cells. (E) Comparative western blots of MET LF and GF OR cells. MET-silenced OR cells revealed a clear reduction in the expression of MET, phosphorylated forms of MET and Akt (p-MET and p-Akt respectively), β-catenin, and Snail while the opposite was observed in the MET overexpressing (GF) counterparts. (F) CAF co-cultured with MET LF OR cells secreted a significantly lower IL-6 into the culture medium as compared to MET GF OR cells. **P<0.01, ***P<0.001.