青蒿琥酯诱导胃癌BGC-823细胞死亡的实验研究

Effects of artesunate on transplanted human gastric cancer BGC-823 in nude mice

目的观察青蒿琥酯(ART)对胃癌细胞株BGC-823的裸鼠移植瘤生长的影响,并探讨其可能的作用机制。方法将胃癌BGC-823细胞注射至裸鼠右侧背部近腋下部位皮下,建立荷瘤裸鼠模型并随机分为空白对照组(0mg/kg ART组)、60mg/kg ART组、120mg/kg ART组、240mg/kg ART组,每组5只。各组裸鼠每天腹腔注射ART1次(空白对照组注射0.9%氯化钠溶液),连续15d,观察裸鼠移植瘤生长情况,并采用RT-PCR、免疫组化及Western blot法测定血管内皮生长因子(VEGF)及钙中性蛋白酶2(Calpain2)表达情况。结果 4组裸鼠移植瘤体积比较有统计学差异(P<0.05),两两比较亦有统计学差异(均P<0.05),与空白对照组比较,60mg/kg ART组、120mg/kg ART组、240mg/kg ART组裸鼠移植瘤体积均明显缩小,ART表现出剂量依赖性的抑瘤作用。4组胃癌BGC-823细胞VEGF、Calpain2 mRNA与蛋白表达水平比较均有统计学差异(均P<0.05),两两比较亦有统计学差异(均P<0.05),与空白对照组比较,60 mg/kg ART组、120 mg/kg ART组、240 mg/kg ART组细胞VEGF mRNA与蛋白相对表达水平均下降,Calpain2 mRNA与蛋白相对表达水平均升高,且VEGF相对表达水平随ART浓度升高而降低,而Calpain2相对表达水平随ART浓度升高而升高。结论 ART在胃癌移植瘤模型体内起剂量依赖性的抑瘤作用,该作用机制可能与下调VEGF的表达、上调Calpain2的表达有关。

Objective To investigate the effect of artesunate on transplanted human gastric cancer in nude mice.Methods Human gastric cancer BGC-823 cells were inoculated in nude mice.The tumor-bearing nude mice were treated with artesunate at a dose of 60,120,or 240 mg/ （kg·d）,i.p.for 15 d.The changes of body weights and tumor size were observed.The expression of VEGF and Calpain2 mRNA and proteins were detected by RT-PCR,immunohistochemical and Western Blot,respectively.Results Artesunate suppressed BGC-823 tumor growth in nude mice in a dose-dependent manner.The expression of VEGF mRNA and protein were decreased and the expression of Calpain2 mRNA and protein were increased in cancer cells of artesunate-treated nude mice,compared to control group （P 〈0.05）.Conclusion Artesunate induces a dose-dependent suppression of BGC-823 tumor growth in nude mice,which might be related to the down-regulation of VEGF and the up-regulation of Calpain2.