人参皂苷Rg3和PEG-PLGA-Rg3纳米微粒抑制肺癌血管新生的体内实验研究

Research of 20(R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles on the angiogennesis of lung cancer in vivo

目的:观察人参皂苷Rg3(Rg3)和PEG-PLGA-Rg3纳米微粒(Rg3-N)在体内对肺癌血管生成的影响并比较二者之间的差异。方法:建立小鼠Lewis肺癌动物模型并随机分为5组:正常对照(C)组、0.9%氯化钠溶液(NS)组、PEG-PLGA纳米载体(PEG)组、Rg3单体(Rg3)组和Rg3纳米微粒(Rg3-N)组,比较Rg3和Rg3纳米微粒对MVD的影响,并检测相关血管新生和炎性因子的水平来探讨它们抗血管生成作用的内在分子机制。结果:Rg3组和Rg3-N组的MVD与NS组相比明显下降(P<0.01),但是Rg3组和Rg3-N组之间未见显著性差异。同时,Rg3组和Rg3-N组的血管内皮生长因子(VEGF)mRNA、基质金属蛋白酶-9(MMP-9)、低氧诱导因子-1α(HIF-1α)降低;VEGF的蛋白表达及白介素-1(IL-1)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)炎性因子的水平显著下降(P<0.05,P<0.01),且Rg3-N组相对于Rg3组有进一步降低的趋势。结论:Rg3和Rg3纳米缓释微粒可在体内抑制肿瘤血管的生成,这种抑制作用可能是通过抑制MMP-9、HIF-1α、VEGF的表达、降低IL-1、IL-6、TNF-α的水平来实现的;PEG-PLGA纳米载体包埋Rg3能提高其在体内抗肿瘤血管生成的能力。

Objective： To observe the effect of 20（R）-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles on the angiogennesis of lung cancer in vivo and analyse the difference between of them. Methods： Lewis lung cancer mice model were established and randomly divided into 5 groups： normal control group （C）, saline control group （NS）, PEG-PLGA group （PEG）, Rg3 group （Rg3）, PEG-PLGA-Rg3 nanoparticles group （Rg3-N）. Therefore, the effect of 20（R）-ginsenoside Rg3 and PEG-PLGA- Rg3 nanoparticles on MVD were analysed. Furthermore, the expression of the relative angiogenic and inflammatory cytokines were examined to explore the internal molecular mechanisms. Results： Compared to NS group, MVD in Rg3 group and Rg3-N group declined significantly （P〈0.01）, even if there was no significant difference between Rg3 group and Rg3-N group. At the same time, the level of VEGF mRNA, the protein expression of MMP-9, HIF-lct, VEGF as well as the level of IL-1, IL-6 and TNF-α in Rg3 group and Rg3-N group decreased compared to NS group （P〈0.05）. Furthermore, the level of Rg3-N group was lower than that of Rg3 group. Conclusion： Rg3 and PEG-PLGA-Rg3 nanoparticles could supress the tumor angiogenesis in vivo, which is perhaps related to the inhibition of expression in MMP-9, HIF-1α, VEGF, IL-1, IL-6 and TNF-α. The PEG-PLGA nanoparticles could improve Rg3＇s ability on inhibiting the tumor angiogenesis in vivo.