Oxymatrine inhibits non–small cell lung cancer via suppression of EGFR signaling pathway

Abstract

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.

For the first time we discovered that oxymatrine inhibited the activation of both wild-type and mutant epidermal growth factor receptor (EGFR). Mechanism studies demonstrated that the inhibition of cell proliferation by oxymatrine was mainly attributed to its effect on EGFR-Akt-cyclin D1 signaling pathway.

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