人参皂苷免疫纳米对胃癌荷瘤裸鼠侵袭转移及VEGF-C、TGF-β1表达的影响

发布时间：2018-09-05 07:33

【摘要】：目的：建立裸鼠原位荧光胃癌模型,探讨人参皂苷免疫纳米(VEGFR3-mediated immune-nanoemulsion of ginsenoside Rg3, VRIN)对人胃癌裸鼠原位移植瘤转移及胃癌裸鼠血清中血管内皮生长因子-C (Vascular endothelial growth factor-C, VEGF-C)、转化生长因子-β1 (Transforming growth factor-beta1, TGF-β1)表达的影响。方法：利用稳定表达红色荧光的细胞系NUGC-4胃癌细胞成功建立裸鼠原位荧光胃癌模型。造模后第9天,将32只人胃癌移植瘤裸鼠随机分成4组,每组8只,分别予生理盐水、5-FU、VRIN低剂量、VRIN高剂量进行干预,观察各组移植瘤裸鼠生存状态及肿瘤转移情况。实验终点处死小鼠,切开胸腹,在开放荧光体视显微镜下检查移植瘤转移情况,计算转移率,并留取原位移植瘤和转移瘤组织行病理检查。酶联免疫吸附试验(Enzyme-Linked ImmunoSorbent Assay, ELISA)检测裸鼠血清中VEGF-C、TGF-β1表达。结果：1、成功建立裸鼠原位荧光胃癌模型,部分裸鼠出现转移,生理盐水组、5-FU组、VRIN低剂量组、VRIN高剂量组的转移率分别为：87.5%、50%、37.5%和12.5%。VRIN高剂量组和生理盐水组比较,有统计学上的意义(P0.05)。2、5-FU组、VRIN低剂量组、VRIN高剂量组均能明显降低胃癌血清中VEGF-C、TGF-p1的表达,与生理盐水组对照均具有显著统计学意义(P0.05)。其中尤以5-FU组、VRIN高剂量组下调VEGF-C、TGF-β1的表达较为明显,与VRIN低剂量组相比有显著统计学意义(P0.05)。VRIN高剂量组与5-FU组比较,无统计学意义(P0.05)。VEGF-C、TGF—β1在发生转移胃癌裸鼠组中的表达显著高于未转移组(P0.05)。结论：1.用稳定表达红色荧光的细胞系NUGC-4胃癌细胞成功建立裸鼠原位荧光胃癌模型,人参皂苷免疫纳米(VRIN)能显著抑制人胃癌裸鼠原位移植瘤转移。2. VEGF-C、TGF-β1水平与胃癌的转移密切相关；VRIN能显著下调胃癌裸鼠血清中VEGF-C、TGF-β1的水平,可能是其抑制胃癌转移的机制。
[Abstract]:Objective: to establish an in situ fluorescence gastric cancer model in nude mice. Objective: to investigate the effects of ginsenoside immune nanoparticles (VEGFR3-mediated immune-nanoemulsion of ginsenoside Rg3, VRIN) on the expression of vascular endothelial growth factor-C (Vascular endothelial growth factor-C, VEGF-C and transforming growth factor-尾-1 (Transforming growth factor-beta1, TGF- 尾 _ 1 in the serum of nude mice with human gastric cancer after orthotopic transplantation. Methods: the in situ fluorescence gastric cancer model of nude mice was successfully established by using NUGC-4 gastric cancer cell line which expressed red fluorescence stably. On the 9th day after modeling, 32 nude mice were randomly divided into 4 groups, each group (n = 8), which were treated with saline 5-FUU VRIN low dose and high dose VRIN, respectively, to observe the survival status and tumor metastasis of nude mice in each group. The mice were sacrificed at the end of the experiment. The tumor metastasis was examined under the open fluorescence stereoscopic microscope and the metastasis rate was calculated. The orthotopic transplanted tumor and the metastatic tumor tissue were taken for pathological examination. Enzyme linked immunosorbent assay (Enzyme-Linked ImmunoSorbent Assay, ELISA) was used to detect the expression of VEGF-C,TGF- 尾 1 in nude mice serum. Results one of the nude mice successfully established an in situ fluorescent gastric cancer model. Some of the nude mice showed metastasis. The metastatic rates of the low dose 12.5%.VRIN group and the 12.5%.VRIN high dose group were 37. 5% and 37. 5%, respectively, compared with those of the normal saline group. There was statistical significance (P0.05). 2FU low dose group could significantly reduce the expression of VEGF-C,TGF-p1 in the serum of gastric cancer (P0.05), and normal saline group had significant statistical significance (P0.05). The down-regulation of VEGF-C,TGF- 尾 _ 1 expression was more obvious in the 5-FU group than in the VRIN low-dose group (P0.05). The expression of VEGF-C,TGF- 尾 _ 1 in the high-dose VRIN group was significantly lower than that in the 5-FU group. The expression of TGF- 尾 1 in metastatic gastric cancer group was significantly higher than that in non-metastasis group (P0.05). Conclusion 1. NUGC-4 gastric cancer cell line with stable expression of red fluorescence was successfully used to establish nude mice model of in situ fluorescence gastric cancer. Ginsenoside immunized nano (VRIN) could significantly inhibit the metastasis of human gastric cancer xenografts in nude mice. The level of VEGF-C,TGF- 尾 1 was closely related to the metastasis of gastric cancer. The level of VEGF-C,TGF- 尾 1 in serum of nude mice with gastric cancer was significantly down-regulated by VEGF-C,TGF- 尾 1, which may be the mechanism of inhibiting the metastasis of gastric cancer.
【学位授予单位】：南京中医药大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R735.2

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