siRNA 抑制胃腺癌VEGF2C 表达和淋巴管生成
Inhibition of Gastric Carcinoma Lymphangiogenesis with Small Interfering RNA Against VEGF2C
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摘要: 目的 研究瘤内注射VEGF2C siRNA 抑制胃癌移植瘤VEGF2C 表达和肿瘤淋巴管生成的有效性。方法 建立裸鼠胃癌皮下移植瘤模型随机分为4 组:VEGF2C siRNA 脂质体混合液组、单脂质体组、单siRNA 组和PBS 组,对肿瘤进行原位注射干预,记录各实验组肿瘤体积变化,免疫组织化学法检测各实验组肿瘤组织VEGF2C 的表达,并通过抗人CD31 和抗人L YVE21 单克隆抗体检测瘤体内血管和淋巴管生成情况。结果 免疫组化显示干扰组肿瘤细胞VEGF2C 染色减弱,和对照组相比VEGF2C 表达下调68. 3 %( P < 0. 01), 而胃癌组织中淋巴管密度(LVD) 值干预组和对照组分别为3. 2 ±1. 3 、9. 8 ±2. 7, VEGF2C siRNA 干预组LVD 值下降至对照组的32. 7 %( P < 0. 01), 而MVD 值无明显差异( P >0. 05) 。结论 瘤内注射VEGF2C siRNA 能显著下调肿瘤组织内VEGF2C 的表达,有效抑制肿瘤生长和瘤内淋巴管生成,而对肿瘤血管生成无影响。Abstract: Objective To evaluate the inhibitory effect s of VEGF2C siRNA on VEGF2C expression and tumor lymphangiogenesis in nude mice SGC7901 subcutaneous xenograf t tumor models. Methods The nude mice model was divided randomly into 4 group s ( n = 6) : VEGF2C siRNA2liposome2suspension, lipo2 some only, siRNA only, and PBS injection. Af ter injection int ratumorally of every group the accumulation of tumor volume of each group was obtained. The expression of VEGF2C in tumor tissue was measured by Immunohistochemist ry ( IHC) . And the status of Angiogenesis and Lymphangiogenesis were examined by IHC staining with anti2CD31 monoclonal antibody and anti2L YVE21 monoclonal antibody. Results The expression of VEGF2C in the VEGF2C siRNA group was down regulated to 68. 3 %( P < 0. 01) compared with cont rol group. The LVD value of interference group and cont rol group was 3. 2 ±1. 3 and 9. 8 ±2. 7 respectively, reduced to 32. 7 %( P < 0. 01) of that in cont rol group. But there is no obviously variance in MVD value between interference group and cont rol group ( P > 0. 05) . Conclusion The VEGF2C siRNA can dramatically down regulated expression of VEGF2C in tumor tissue. And it lead to inhibition of tumor growth and tumor Lymphangiogeneis, but no effect on angiogenesis.
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