摘要
目的:探讨蒿甲醚(artemether,ART)在体外以及荷瘤小鼠体内对于人胃癌SGC-7901细胞的杀伤作用及增殖抑制作用及具体机制.方法:采用MTT法检测不同浓度ART在体外环境下对于人胃癌细胞株SGC-7901的抑制作用,采用流式细胞术对经过不同浓度的A RT处理后的人胃癌S G C-7901细胞进行细胞周期分析,检测凋亡情况.建立人胃癌裸鼠移植瘤模型,通过计算肿瘤体积和抑瘤率探讨ART在荷瘤裸鼠体内的抗肿瘤作用.利用Western blot方法探讨ART抑制肿瘤细胞生长增殖的具体机制.结果:MTT结果显示,相比于对照组ART对该株肿瘤细胞具有显著的杀伤作用(P<0.05),分析应用的A RT变化、作用时间和细胞不良反应变化关系发现,ART对于人胃癌细胞株SGC-7901杀伤作用呈现时间依赖和剂量依赖特性(P<0.05);FCM检测结果表明,ART抑制癌细胞增殖的机制主要是在于阻滞细胞周期进程,使其细胞周期停滞于G0/G1期和诱导细胞凋亡;与对照组比较,中、高剂量ART组对人胃癌S G C-7901细胞裸鼠移植瘤的生长抑制效果最明显(P<0.05),抑瘤率分别为34.5%和41.0%.Westernblot法检测发现A R T处理后细胞增殖细胞核抗原(proliferating cellnuclearantigen,P C N A)、B淋巴细胞瘤-2基因(B-cell lymphoma-2,Bcl-2)蛋白表达量下降,Bcl-2相关X蛋白(Bcl-2associated X protein,Bax)蛋白表达量上升(P<0.05).结论:ART对人胃癌细胞株SGC-7901有较明显的细胞毒效应,且具有时间依赖性和剂量依赖性;其抑制作用与阻滞细胞周期进程和诱导细胞凋亡有关.ART对人胃癌SGC-7901细胞裸鼠移植瘤的生长具有明显的抑制作用,ART阻滞细胞周期进程和诱导细胞凋亡可能与抑制PCNA、Bcl-2蛋白表达,促进Bax蛋白表达相关.
AIM： To investigate the inhibitory effect of artemether（ART） on cell proliferation and apoptosis in human gastric adenocarcinoma cell line and tumor growth in tumor bearing mice. METHODS： The inhibitory effect of ART on cell proliferation in human gastric cancer cell line SGC-7901 was detected by MTT assays, and the effects on cell cycle and apoptosis were evaluated by flow cytometry. The anti-tumor effect of ART was observed in tumor bearing nude mice by measuring mice weight and diameter and calculating tumor volume and tumor growth inhibition rate. The mechanism underlying the effects of ART on cell proliferation and apoptosis was explored by Western blot. RESULTS： MTT assays showed that ART inhibited SGC-7901 cell growth in a time- and dosage-dependent manner（P 〈 0.05）. The results of flow cytometry demonstrated that ART treatment induced cell arrest at G0/G1 phase and cell apoptosis. Medium- and high-dose ART had significant anti-tumor effects in human gastric cancer cell bearing mice, and the inhibition rates were 34.5% and 41.0%, respectively. ART treatment up-regulated proliferating cell nuclear antigen（PCNA） and B-cell lymphoma-2（Bcl-2） expression, and down-regulated Bcl-2 associated X protein（Bax） expression（P 〈 0.05）. CONCLUSION： ART can inhibit proliferation and induce arrest cell cycle and apoptosis in SGC-7901 cells in vitro as well as tumor growth in vivo.
出处
《世界华人消化杂志》
CAS
2015年第4期590-595,共6页
World Chinese Journal of Digestology
