Oxymatrine inhibits non-small cell lung cancer via suppression of EGFR signaling pathway.
Wei LiXinfang YuShiming TanWenbin LiuLi ZhouHaidan LiuPublished in: Cancer medicine (2017)
Epidermal growth factor receptor (EGFR) plays a crucial role in human non-small cell lung cancer (NSCLC) tumorigenesis. In this study, oxymatrine was identified as an EGFR signaling pathway inhibitor in NSCLC. Oxymatrine inhibited anchorage-dependent and independent growth of NSCLC cell lines but had no cytotoxicity in normal lung cells. We found that exposure to oxymatrine not only suppressed the activity of wild-type EGFR but also inhibited the activation of exon 19 deletion and L858R/T790M mutated EGFR. Flow cytometry analysis suggested that oxymatrine-induced cell cycle G0/G1 arrest was dependent on EGFR-Akt signaling. Exogenous overexpression of Myr-Akt rescued cyclin D1 expression in HCC827 cells. Moreover, oxymatrine prominently suppressed tumor growth in a xenograft mouse model. Thus, oxymatrine appears to be a novel therapeutic agent for NSCLC treatment.
Keyphrases
- epidermal growth factor receptor
- small cell lung cancer
- advanced non small cell lung cancer
- cell cycle
- signaling pathway
- tyrosine kinase
- induced apoptosis
- cell proliferation
- pi k akt
- cell cycle arrest
- brain metastases
- flow cytometry
- wild type
- mouse model
- endothelial cells
- epithelial mesenchymal transition
- high glucose
- long non coding rna