MET/PKCß expression correlate with metastasis and inhibition is synergistic in lung cancer

Background: Treatment of non-small cell lung cancer (NSCLC) remains a difficult task in oncology. Targeted inhibition of oncogenic proteins is promising. In this study, we evaluate the expression of MET and PKCs and in vitro effects of their inhibition using SU11274 and enzastaurin (LY317615.HCl) respectively. Materials and Methods: Patient samples were analyzed by immunohistochemistry for expression of PKCs and MET, utilizing tissue microarrays under an IRB-approved protocol. Expression of PKCs and MET was evaluated in cell lines by immunoblotting. Treatment with SU1174 against MET and enzastaurin against PKCs was performed in H1993 and H358 cell lines, and cell proliferation and downstream signaling (phosphorylation of MET, AKT, FAK, and GSK3s) were evaluated by immunoblotting. Statistical analysis was performed using SPSS 16.0. Results: Expression of MET positively correlated with lymph node metastases (p=.0004), whereas PKCs showed no correlation (p=0.204). MET and PKCs expression were also strongly correlated (p Conclusions: Concomitant inhibition of MET and PKCs significantly increased cytotoxicity in vitro against NSCLC, disrupting important downstream signaling pathways. Further evaluation in animal models is warranted.