氧化苦参碱靶向表皮生长因子受体（磷酸化酪氨酸845位点）并抑制表皮生长因子受体相关信号通路，以抑制胃癌细胞的增殖和侵袭。

Oxymatrine targets EGFR(p-Tyr845) and inhibits EGFR-related signaling pathways to suppress the proliferation and invasion of gastric cancer cells.

作者信息

Guo Bingyu, Zhang Tingting, Su Jingyuan, Wang Kaiwen, Li Xiaoming

机构信息

Institute of Neurology, General Hospital of Shenyang Military Command, 83#Wenhua Road, Shenhe District, Shenyang, 110016, Liaoning, China.

出版信息

Cancer Chemother Pharmacol. 2015 Feb;75(2):353-63. doi: 10.1007/s00280-014-2651-1. Epub 2014 Dec 20.

DOI:10.1007/s00280-014-2651-1

PMID:25527205

Abstract

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 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.

CONCLUSION

Oxymatrine effectively suppressed the phosphorylation of EGFR (Tyr845), and EGFR was the target of oxymatrine.

摘要

目的

氧化苦参碱（苦参碱氧化物、苦参碱N-氧化物、苦参碱1-氧化物）是从传统中草药苦参根中提取的喹诺里西啶生物碱化合物之一。氧化苦参碱对多种癌细胞具有化疗耐药性和细胞毒性作用，但其潜在机制尚未得到探索。我们研究氧化苦参碱对胃细胞的作用机制。

方法

通过检测氧化苦参碱发挥作用的信号通路，观察人胃细胞增殖、凋亡和侵袭的变化。

结果

这些结果表明，氧化苦参碱通过抑制EGFR（p-Tyr845），抑制EGFR/Cyclin D1/CDK4/6、EGFR/Akt和MEK-1/ERK1/2/MMP2通路，从而抑制胃细胞的增殖和侵袭。除诱导胃细胞凋亡外，氧化苦参碱通过降低磷酸化Cofilin（Ser3）和磷酸化LIMK1（Thr508），显著抑制人胃癌细胞的迁移和侵袭，而不改变总Cofilin和LIMK1的表达。