Expression and pharmacological inhibition of thymidylate synthase and Src kinase in nonsmall cell lung cancer

摘要: The combination of cytotoxic chemotherapy with signaling pathway inhibitors represents a potential strategy to improve the treatment nonsmall cell lung cancer (NSCLC). Thymidylate synthase (TS) is an enzyme essential for DNA synthesis, and its overexpression has been associated reduced sensitivity antifolate agents. Src tyrosine kinase that modulates cytotoxicity cells after drug treatment, in vitro data indicate inhibition could revert resistance TS-inhibiting drugs. Our study investigated significance TS expression NSCLC tissues, effects their pharmacological lines. In tumor normal tissues from 94 resected patients, transcript levels were found positively correlated (RS = 0.66), patients smoking history overall survival. At multivariate analysis, gene was independent prognostic factor (relative risk (RR) 1.78, 1.16 2.72; p < 0.01). Immunohistochemical detection specimens confirmed activation, evaluated by phospho-specific antibody, higher expression. lines, dasatinib, Src-inhibiting agent, synergistically enhanced pemetrexed-cytotoxicity A549 cells, as MTT apoptosis assays. biological explanation this interaction based on upregulation messenger RNA protein induced pemetrexed, which significantly prevented dasatinib cotreatment. our suggest may belong common bears NSCLC, target efficacy