纳米雄黄抑制A431细胞株新生血管的机制研究
李秀荣1,李慧杰2,林艳艳2
Experimental research of realgar nanoparticles on neovascularization suppression of cu-taneous squamous cell carcinoma
Li Xiurong1,Li Huijie2,Lin Yanyan2
1The Affiliated Hospital of Shandong University of TCM,Shandong Jinan250011,China;2Shandong University of TCM,Shandong Jinan 250014,China.
【Abstract】Objective:To study the inhibition on growth of blood vessels of human skin squamous cell carcinoma
A431cells with nanometer realgar treatment.Methods:Cultured the skin squamous cell carcinoma A431cells in
vitro,then detect the expression of pigment epitheliun-deriwed factor(PEDF)and VEGF mRNA by immunohisto-
chemical staining and RT-PCR method with different concentrations of nanometer realgar processing.Results:In
control group,5%,15%,25%realgar nanoparticles group,DDP group,integrated group of A431cells,PEDF expres-
sion positive rates were(21.50?2.28)%,(28.81?2.75)%,(42.23?2.35)%,(56.80?3.80)%,(46.33?
2.07)%,(59.82?4.80)%;VEGF mRNA relative expression levels((86.30?6.44)%,72.45?5.37)%,(52.74
?7.21)%,(44.81?4.34)%,(30.92?4.12)%,(18.35?5.09)%.By the nanometer realgar,human skin squa-
mous cell carcinoma A431cells PEDF significantly higher generation of VEGF transcriptional mRNA levels were sig-
nificantly lower,showed a dose-dependent with cisplatin.Conclusion:The vitro experiments showed that realgar
nanoparticles can inhibit the proliferation of A431cells related with increase the expression of PEDF and downregula-
tion of the expression of VEGF to inhibit angiogenesis.
【Key words】realgar nanoparticles;skin squamous cell carcinoma A431cells;tumor angiogenesis;PEDF;VEGF
Modern Oncology2013,21(02):0232-0234
【摘要】目的:探讨纳米雄黄抑制人皮肤鳞癌A431细胞新生血管的作用及其相关机理。方法:对皮肤鳞癌
A431细胞进行体外培养,分别采用免疫组织化学法和RT-PCR法检测不同浓度纳米雄黄处理后其色素上皮
源性因子(PEDF)和VEGF mRNA的表达情况。结果:对照组、5%、15%、25%纳米雄黄组、DDP组、综合组
A431细胞PEDF表达阳性率分别为(21.50?2.28)%、(28.81?2.75)%、(42.23?2.35)%、(56.80?
3.80)%、(46.33?2.07)%、(59.82?4.80)%;VEGF mRNA相对表达量为(86.30?6.44)%、(72.45?
5.37)%、(52.74?7.21)%、(44.81?4.34)%、(30.92?4.12)%、(18.35?5.09)%。可见,经纳米雄黄作用
后,人皮肤鳞癌A431细胞PEDF的生成量明显升高,VEGF转录mRNA水平显著降低,均呈剂量依赖性,与顺
铂联合有协同作用。结论:体外实验表明纳米雄黄抑制A431新生血管生成的作用可能与上调PEDF的表达
和下调VEGF的表达有关。
【关键词】纳米雄黄;皮肤鳞癌A431细胞;肿瘤血管生成;PEDF;VEGF
【中图分类号】R73-36;R739.5【文献标识码】A DOI:10.3969/j.issn.1672-4992.2013.02.03
【文章编号】1672-4992-(2013)02-0232-03
【收稿日期】2012-07-05
【修回日期】2012-07-19
【基金项目】山东省自然科学基金资助项目(编号:ZR2010HL050)【作者单位】1山东中医药大学附属医院,山东济南250011
2山东中医药大学,山东济南250014
【作者简介】李秀荣(1963-),女,山东济南人,主任医师,博士生导师,从事中西医结合肿瘤防治研究。E-mail:lixr@
126.com
【通讯作者】李慧杰(1982-),女,河北廊坊人,在读博士,从事中西医结合肿瘤防治研究。E-mail:2008lihuijie@163.
com
皮肤鳞状细胞癌(squamouseellcareinoma,SCC)起源于表皮或附属器角质形成细胞。其发病率逐年上升,可发生淋巴结、肺转移,成为威胁人类生命的恶性肿瘤之一[1]。皮肤鳞癌的发生涉及基因突变及修复损伤导致各种调控因子的缺失或过度表达,其中包括与细胞凋亡、增殖分化及新生血管生成等调控因子的表达异常。中药雄黄主要成分包括As2S2或As4S4并夹杂少量As2O3和其他重金属盐,现代研究表明,雄黄具有杀菌、消炎镇痛和抗肿瘤等作用[2]。徐辉碧教授等提出了纳米雄黄这一概念,将传统雄黄纳米化后,粒径减小,药效增强,毒副作用减低[3]。本文主要通过检测纳米雄黄对人皮肤鳞癌A431细胞血管内皮生长因子和血管抑制
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·李秀荣,等纳米雄黄抑制A431细胞株新生血管的机制研究