大黄素通过调节TGF-β1、Smad4抑制人胰腺癌的血管生成
投稿时间:2017-02-16  修订日期:2017-02-23  点此下载全文
引用本文:徐锦波,陈敏远,徐宏涛.大黄素通过调节TGF-β1、Smad4抑制人胰腺癌的血管生成[J].医学研究杂志,2017,46(10):162-165
DOI: 10.11969/j.issn.1673-548X.2017.10.040
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作者单位E-mail
徐锦波 323000 丽水市中心医院  
陈敏远 323000 丽水市中心医院  
徐宏涛 323000 丽水市中心医院 xujinbo0108@163.com 
中文摘要:目的 探讨大黄素是否抑制胰腺癌的血管生成及其机制。方法 建立胰腺癌SW1990细胞裸鼠原位移植瘤动物模型(SOI),分为对照组(N组)、20mg/kg大黄素组(E20组)、40mg/kg大黄素组(E40组)和80mg/kg大黄素组(E80组)。采用免疫组织化学染色法检测肿瘤组织CD34的表达,从而确定其微血管密度(MVD)。通过RT-PCR法分析肿瘤新生血管相关的TGF-β1、Smad4因子的表达,Western blot法分析肿瘤新生血管相关的TGFβ1、Smad4的表达。结果 免疫组织化学染色显示大黄素组MVD比对照组均显著减少,而且MVD与大黄素用药浓度呈负相关。大黄素降低TGF-β1的mRNA表达水平,并且与剂量呈负相关,E40和E80相对于对照组水平显著降低(P<0.05)。同时,大黄素明显增加Smad4基因mRNA的表达水平。Smad4基因在E20、E40和E80组相对于对照组均显著提高(P<0.05)。Western blot法与mRNA水平的差异相符合,不同剂量的大黄素较对照组上调Smad4在胰腺癌组织中的相对蛋白水平(P<0.05),而下调了TGF-β1的蛋白表达。结论 大黄素对裸鼠体内人胰腺癌SW1990细胞原位移植瘤的新生血管抑制作用效果显著。其机制可能是大黄素改变新生血管相关的TGF-β1、Smad4的表达有关。
中文关键词:大黄素  胰腺癌  新生血管  TGF-β1  Smad4
 
Emodin Inhibits the Angiogenesis of Pancreatic Cancer by Regulating the TGF-β1 and Smad4
Abstract:Objective To investigate whether emodin suppresses angiogenesis in pancreatic cancer. Methods A nude mouse pancreatic cancer xenograft model was established with SW1990 human pancreatic cancer cells by surgical orthotopic implantation. Different doses of emodin were injected into the abdominal cavities of the tumor-bearing mouse models and controls 3 times weekly for 2 weeks. The expression of CD34 was detected by immunochemistry, and microvessel density was calculated.Quantitative RT-PCR and Western blot were performed to determine the mRNA and protein expressions of TGF-β1 and Smad4. Results A negative dose-dependent association was found among emodin treatments about the weight of tumors. Emodin was associated with lower levels of TGF-β1 mRNA and protein, and higher levels of the mRNAs and proteins Smad4. Conclusion Emodin may repress angiogenesis in pancreatic cancer by altering activities of the TGF-β1 and Smad4.
keywords:Emodin  Pancreatic cancer  Angiogenesis  TGF-β1  Smads
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