Targeting the COX2/MET/TOPK signaling axis induces apoptosis in gefitinib-resistant NSCLC cells.

ABSTRACT: MET overactivation is one of the crucial reasons for tyrosine kinase inhibitor (TKI) resistance, but the mechanisms are not wholly clear. Here, COX2, TOPK, and MET expression were examined in EGFR-activating mutated NSCLC by immunohistochemical (IHC) analysis. The relationship between COX2, TOPK, and MET was explored in vitro and ex vivo. In addition, the inhibition of HCC827GR cell growth by combining COX2 inhibitor (celecoxib), TOPK inhibitor (pantoprazole), and gefitinib was verified ex vivo and in vivo. We found that COX2 and TOPK were highly expressed in EGFR-activating mutated NSCLC and the progression-free survival (PFS) of triple-positive (COX2, MET, and TOPK) patients was shorter than that of triple-negative patients. Then, we observed that the COX2-TXA₂ signaling pathw

SUBMITTER: Xiao J 

PROVIDER: S-EPMC6791885 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature