An oral DNA vaccine against VEGFR2 inhibits angiogenesis of Lewis lung carcinoma in C57BL/6 mice

Abstract

血管内皮生长因子（VEGF）及其主要受体血管内皮生长因子受体-2（VEGFR2）在肿瘤新生血管和肿瘤基质形成过程中起着重要作用。本研究的目的是观察口服VEGFR2 DNA疫苗抗C57BL/6小鼠Lewis肺癌皮下移植瘤生长的作用,并探讨其可能的作用机制。方法 将重组DNA疫苗对小鼠进行免疫,通过观察小鼠Lewis肺癌皮下移植瘤大小,记录各组小鼠离体肿瘤湿重,检测移植瘤微血管密度（MVD）及血液CD3+、CD8+T细胞水平,评价重组疫苗的抑瘤作用。结果 疫苗组、空质粒组、生理盐水组的MVD分别为1.75±1.07、6.89±2.52、7.57±3.75,肿瘤湿重分别为（2.05±1.32）、（4.83±1.47）、（5.12±1.02）g,疫苗组与其它两组比较,差异均有统计学意义（P < 0.05）。接种肿瘤后,疫苗组CD3+T细胞仍维持较高水平,其它两组明显下降（P < 0.05）;疫苗组CD8+T细胞水平较其它两组明显升高（P < 0.05）。结论 口服VEGFR2DNA疫苗对小鼠Lewis肺癌皮下移植瘤的生长具有较强的抑制作用。该疫苗可能是通过杀伤肿瘤内皮细胞、抑制血管生成而起到抗肿瘤生长的作用。

Background and objective It has been known that vascular endothelial growth factor （VEGF） and its receptor （VEGFR2） play important roles in tumor angiogenesis. The aim of this study is to investigate whether an oral DNA vaccine against VEGFR2 has the inhibition effect on tumor growth and angiogenesis, and explore its mechanism in vivo. Methods C57BL/6 mice were respectively given the DNA vaccine encoding VEGFR2 （vaccine group）, pcDNA3.1 （plasmid group） and saline （saline group）. All the mice were then inoculated with Lewis lung carcinoma 3LL cells. Weight, size and microvessel density （MVD） of transplanted tumors were observed. The levels of CD3+ and CD8+ T cells in peripheral blood of mice were detected by flow cytometry. Results Weight of transplanted tumors in vaccine group was significantly smaller than those in plasmid and saline groups （P < 0.05）, and MVD was significantly lower in vaccine group than that in plasmid and saline groups （P < 0.05）. After inoculated with 3LL cells, CD3+ and CD8+ T cell levels of vaccine group were markedly higher than those of plasmid and saline groups （P < 0.05）. Conclusion The oral DNA vaccine can significantly inhibit angiogenesis and growth of transplanted tumor in mice. It may act through killing endothelial cells of tumor.