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青蒿琥酯通过促进体外和体内细胞胀亡的机制抑制胃癌细胞的生长。

Artesunate inhibits the growth of gastric cancer cells through the mechanism of promoting oncosis both in vitro and in vivo.

机构信息

Department of Surgery, The Second Affiliated Hospital of Wenzhou Medical University, People's Republic of China.

出版信息

Anticancer Drugs. 2013 Oct;24(9):920-7. doi: 10.1097/CAD.0b013e328364a109.

Abstract

This study aims to investigate the significance and mechanism of artesunate involved in suppressing the proliferation of gastric cancer in vitro and in vivo. In the in-vitro experiments, artesunate inhibited the growth of gastric cancer cell lines (SGC-7901, BGC-823, and AGS) with concentration-dependent activity, with no significant effect on GES-1 cells. BGC-823 cells treated with artesunate showed the typical morphologic features of oncosis rather than apoptosis. Meanwhile, we observed calcium overload, downregulation of vascular endothelial growth factor expression, and upregulation of calpain-2 expression in the artesunate-treated BGC-823 cells. In addition, the in-vivo study showed that artesunate produced a dose-dependent tumor regression in nude mice. The antitumor activity of 240 mg/kg artesunate was similar to that of 10 mg/kg docetaxel. Furthermore, compared with the control group, no significant difference was observed in the body weight of artesunate-treated nude mice other than docetaxel-treated nude mice. These observations show that artesunate has concentration-dependent inhibitory activities against gastric cancer in vitro and in vivo by promoting cell oncosis through an impact of calcium, vascular endothelial growth factor, and calpain-2 expression.

摘要

本研究旨在探讨青蒿琥酯在体外和体内抑制胃癌增殖的意义和机制。在体外实验中,青蒿琥酯对胃癌细胞系(SGC-7901、BGC-823 和 AGS)的生长具有浓度依赖性抑制作用,对 GES-1 细胞无明显作用。青蒿琥酯处理的 BGC-823 细胞表现出典型的胀亡而非凋亡形态特征。同时,我们观察到青蒿琥酯处理的 BGC-823 细胞中存在钙超载、血管内皮生长因子表达下调和钙蛋白酶-2 表达上调。此外,体内研究表明青蒿琥酯在裸鼠体内产生了剂量依赖性的肿瘤消退。240mg/kg 青蒿琥酯的抗肿瘤活性与 10mg/kg 多西他赛相似。此外,与对照组相比,青蒿琥酯处理的裸鼠体重与多西他赛处理的裸鼠体重无明显差异。这些观察结果表明,青蒿琥酯通过影响钙、血管内皮生长因子和钙蛋白酶-2 的表达,促进细胞胀亡,从而具有体外和体内浓度依赖性抑制胃癌的活性。

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