Oxymatrine targets EGFRp-Tyr845 and inhibits EGFR-related signaling pathways to suppress the proliferation and invasion of gastric cancer cells

Oxymatrine (matrine oxide, matrine N-oxide, matrine 1-oxide) is one of the quinolizidine alkaloid compounds extracted from the root of Sophora flavescens (a traditional Chinese herb). Oxymatrine has been known for its chemoresistance and cytotoxic effects on various cancer cells, but the mechanism underlying has not been explored. We study the mechanism of oxymatrine on gastric cells. We observed the changes of proliferation, apoptosis and invasion in human gastric cells by detecting the signaling pathway in which oxymatrine plays role. These results showed that oxymatrine inhibited the proliferation and invasion of gastric cells through inhibition of EGFR/Cyclin D1/CDK4/6, EGFR/Akt and MEK-1/ERK1/2/MMP2 pathway by inhibiting EGFR(p-Tyr845). In addition to inducing gastric cells apoptosis, oxymatrine significantly inhibited the migration and invasion of human gastric cancer cells by decreasing phospho-Cofilin (Ser3) and phospho-LIMK1 (Thr508) without changing the total Cofilin and LIMK1 expression. Oxymatrine effectively suppressed the phosphorylation of EGFR (Tyr845), and EGFR was the target of oxymatrine.