ABSTRACT
EGFR tyrosine kinase inhibitor (EGFR-TKI)-targeted therapy has been playing an important role in the treatment of non-small cell lung cancer (NSCLC). However, unavoidable therapeutic resistance significantly limits the clinical efficacy of TKI. As an important member of the PAK family of serine/threonine kinases, p21-activated protein kinase 2 (PAK2) plays a critical role in tumorigenesis and tumor development. The aim of this work is to investigate the effect and molecular mechanism of inhibition of PAK2 on the reversal of gefitinib resistance in NSCLC. Firstly, Western blotting was used to detect the expression and phosphorylation level of PAK2 in gefitinib-resistant HCC827/GR cells. The results showed that the phosphorylation level of PAK2 was significantly increased in HCC827/GR cells compared with HCC827 cells (P < 0. 01), while the total protein level of PAK2 did not change. Then, HCC827/GR cells were treated with PAK2 inhibitors FRAX597 or G5555. The MTS assay and clone formation assay results showed that FRAX597 or G5555 significantly increased the sensitivity of HCC827/GR cells to gefitinib (P < 0. 01). Flow cytometry analysis showed that treatment of FRAX597 could induce cell cycle arrest in G