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

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• 作者：Bingyu Guo (1)
  Tingting Zhang (1)
  Jingyuan Su (1)
  Kaiwen Wang (1)
  Xiaoming Li (1)
  
  1. Institute of Neurology ; General Hospital of Shenyang Military Command ; 83#Wenhua Road ; Shenhe District ; Shenyang ; 110016 ; Liaoning ; China
  
• 关键词：Oxymatrine ; Gastric cancer ; EGFR ; Phosphorylation ; Signaling pathway
• 刊名：Cancer Chemotherapy and Pharmacology
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：75
• 期：2
• 页码：353-363
• 全文大小：4,327 KB
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• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Cancer Research
  Pharmacology and Toxicology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0843

文摘

Purpose 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. Methods We observed the changes of proliferation, apoptosis and invasion in human gastric cells by detecting the signaling pathway in which oxymatrine plays role. Results 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 EGFRp-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. Conclusion Oxymatrine effectively suppressed the phosphorylation of EGFR (Tyr845), and EGFR was the target of oxymatrine.