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目的研究腺病毒介导的干扰核糖核酸(RNAi)联合化疗对小鼠肺癌的治疗作用。方法构建表达小鼠血管内皮生长因子(VEGF)序列特异性小干扰RNA(siRNA)复制缺陷型腺病毒(AdH1-siRNA/VEGF)。建立小鼠Lewis肺癌的动物模型,随机均分成五组,分别实施环磷酰胺化疗(A组)、腺病毒治疗(B组)、空载腺病毒处理(C组)、AdH1-siRNA/VEGF病毒联合环磷酰胺处理(D组)和生理盐水对照(E组)。定期测量肿瘤体积,ELISA方法测定VEGF表达,免疫组化法检测肿瘤微血管密度(MVD)。结果 AdH1-siRNA/VEGF可以显著下调肿瘤细胞VEGF的分泌。A、B和D组肿瘤的体积小于E、C组(P<0.05)。B组血清VEGF水平低于C、E组(P<0.01);B、D组肿瘤的MVD低于C、E组(P<0.01)。结论重组腺病毒介导的siRNA技术在体外和体内能有效地下调VEGF的表达,减少肿瘤内微血管生成、抑制肿瘤生长;RNAi联合化疗抗肿瘤活性效果更好。
Objective To study the therapeutic effect of adenovirus-mediated RNA interference (RNAi) combined with chemotherapy on lung cancer in mice. Methods Mouse adenoviral vector (AdH1-siRNA / VEGF) expressing mouse vascular endothelial growth factor (VEGF) sequence-specific small interfering RNA (siRNA) was constructed. The animal model of Lewis lung cancer in mice was established and randomly divided into five groups, which were treated with cyclophosphamide chemotherapy (group A), adenovirus (group B), empty adenovirus (group C), AdH1-siRNA / Combination cyclophosphamide (group D) and saline control group (group E). Tumor volume was measured regularly, VEGF expression was measured by ELISA and tumor microvessel density (MVD) by immunohistochemistry. Results AdH1-siRNA / VEGF can significantly reduce the secretion of VEGF in tumor cells. The tumor volume in groups A, B and D was smaller than that in groups E and C (P <0.05). The level of serum VEGF in group B was lower than that in group C and E (P <0.01). The MVD in group B and D was lower than that in group C and E (P <0.01). Conclusions Recombinant adenovirus mediated siRNA can effectively down-regulate the expression of VEGF in vitro and in vivo, reduce the intra-tumor angiogenesis and inhibit the growth of the tumor. The anti-tumor activity of RNAi combined with chemotherapy is better.