大黄素抑制胰腺癌裸鼠原位移植瘤的实验研究(1)
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摘 要：目的：观察大黄素(Emodin)对胰腺癌裸鼠原位移植瘤生长、转移的抑制作用并探讨其机制。方法：建立胰腺癌裸鼠原位移植瘤模型(SOI),随机分为对照组、实验Ⅰ组、实验Ⅱ组等3组(n10)，第3周开始分别经灌胃给予溶媒(0.1%二甲基亚砜)0.2mL/只、大黄素 20mg/kg、大黄素 40mg/kg，每周3次，共两周。术后第8周处死裸鼠，测量原位肿瘤瘤重并计算抑瘤率；观察荷瘤裸鼠肿瘤转移情况；免疫组织化学法检测肿瘤组织的增殖指数( PI)、微血管密度(MVD)以及金属蛋白酶-9(MMP-9)的表达。结果：与对照组相比，实验Ⅰ组肿瘤生长未受明显抑制，但转移明显被抑制；实验Ⅱ组肿瘤生长和转移均受显著抑制；实验Ⅰ、Ⅱ组肿瘤组织中PI、MVD及MMP-9的表达均明显降低。结论：大黄素具有抑制胰腺癌裸鼠原位移植瘤生长和转移的作用，这可能是通过抑制胰腺肿瘤MMP-9的表达而实现。
关键词：胰腺肿瘤；大黄素；转移
中图分类号：R285.5 文献标识码：A 文章编号：1673-7717(2011)04-0770-03
Abstract:Objective:To investigate the antitumor and anti-metastasis effects of emodin on the model of human pancreatic carcinoma established by surgical orthotopic implantation (SOI) in nude mice. Methods: After 3 weeks of implantation, the SOI model were randomized into 3 groups (n 10): Control group, feed with 0.1% Dmethyl sulfoxide(DMSO)0.2mL/D Test group Ⅰ, Emodin at dose of 20mg/kg Test group Ⅱ, Emodin at dose of 40mg/kg. All treatment lasted for two weeks, thrice per week. Eight weeks after implantation, tumor weight, inhibition rate, and the presence of metastasis were evaluated respectively after the mice were sacrificed. Immunohistochemistry was used to detect the positive expression of ki-67, CD34 and MMP-9 in the tumors. Results:The rate of metastasis in test group Ⅰ was significantly lower than the rate in control group. In test group Ⅱ,both the rate of metastasis and the tumor weight were significantly lower than those in control group. The positive expression of ki-67, CD34 and MMP-9 in the tumors of two test groups were significantly lower than those in control group. Conclusion:Emodin has the antitumor and anti-metastasis effects to the human pancreatic carcinoma in nude mice and those effects may be related to the down-regulation of MMP-9.
Key words:emodin pancreatic neoplasm metastasis
蒽醌类化合物大黄素(Emodin，6-甲基-1，3，8-三羟基蒽醌)为大黄等中药的有效成分，具有如抗炎、抗肿瘤、免疫调节、保护肝脏等多种生物活性作用【sup】[1]【/sup】。具体在抗肿瘤方面，有多个研究表明，大黄素在体外可抑制胰腺癌、卵巢癌、肺癌和白血病等多种恶性肿瘤细胞生长【sup】[2]【/sup】。本研究通过建立胰腺癌裸鼠原位移植模型(SOI)，观察大黄素在裸鼠体内对胰腺原位移植瘤生长、转移的抑制作用及其对肿瘤血管生长的影响，旨在探讨大黄素体内抗胰腺癌的作用及机制。
1 材料与方法
1.1 材料
大黄素(批号：E7881)及溶媒二甲基亚砜(DMSO)均购自美国Sigma公司；胎牛血清(FBS)、含EDTA胰酶和RPMI-1640培养基等购自美国Gibco公司；MMP-9抗体(批号：2551-1)购自美国Epitomics公司；ki-67和CD34抗体购自北京中杉金桥生物技术公司 ......
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