| Objective:Observe the effects of ginsenoside Rg3nanoemulsion on growth, life status and lymph node metastasis in human gastric carcinoma orthotopic transplantation tumor model in nude mice and explore the mechanism of ginsenoside Rg3nanoemulsion in inhibiting lymphatic metastasis of gastric carcinoma by observing its effects on the microlymphatic vessel density(MLVD), the expressions of vascular endothelial growth factor C(VEGF-C) and its receptor vascular endothelial growth factor receptor3(VEGFR-3) in tumor tissue.Methods:A gastric cancer model in nude mice was constructed by surgical orthotopic implantation of human gastric carcinoma cell (NUGC-4) with red fluorescent protein (RFP) expression in nude mice. Twenty-four nude mice were randomly and evenly divided into three groups treated with normal saline,5-Fluorouracil, and ginsenoside Rg3nanoemulsion respectively. The the weight change, food-intake and activity of mice were observed regularly. When experiment was terminated, The mice were sacrificed and dissected, the tumors were weighted, and the inhibition rate was calculated. The tumor metastasis to lymph node was measured by fluorescence imaging and observed by Pathological diagnosis, Lymphatic microvessel density and expression of VEGF-C and its receptor VEGFR-3in tumor mass were measured by immunohistochemistry staining (IHCS) and analyzed semi-quantitatively.Result:1. The food-intake and activity of all groups declined, the weight of Rg3group and saline group increased while the weight of5-Fu group decreased. The life status of5-Fu group were worse than other groups (P<0.05)2. All groups of the orthotopic transplantation tumors in the nude mice were grew well, and some of these mice had lymph node metastasis. The tumors of saline group were the heaviest and largest, while the one of5-FU group were the smallest, the difference had a statistical significance (P<0.05).The Inhibition rate of5-Fu group and Rg3group were69.2%and57.2%.The lymph node metastasis rates of5-Fu group and Rg3group were50%(4/8) and37.5%(3/8), significantly lower than saline group, which was87.5%(7/8)3. The LMVD of saline group was9.29±2.06,5-FU group was6.42±1.38, and Rg3group was5.25±1.08. Compared with normal saline group, the LMVD in Rg3group and5-Fu group were significantly decreased (P<0.05), and the difference between Rg3group and5-Fu group had a statistical significance (P<0.05) as well.4. Compared with saline group, the expressions of VEGF-C、VEGFR-3proteins in Rg3group and5-Fu group were significantly decreased (P<0.05); the expressions of VEGF-C、 VEGFR-3in group which treated with Rg3is lower than that with5-FU. the difference between Rg3group and5-Fu group on VEGF-C had a statistical significance(P<0.05),but the difference on VEGFR-3had no significant difference (P>0.05)Conclusion:1、Ginsenoside Rg3nanoemulsion can inhibit the growth of transplantation tumor in nude mice and improve their life status.2、Ginsenoside Rg3nanoemulsion can obviously inhibit lymph node metastasis of the orthotopic transplantation model of human gastric carcinoma NUGC-4in nude mice.which is more effective than5-FU.3、Ginsenoside Rg3nanoemulsion can down-regulate the expressions of VEGF-C、 VEGFR-3proteins in the tumor tissue and inhibit lymphangiogenesis, which may be the mechanism of ginsenoside Rg3nanoemulsion in inhibiting lymphatic metastasis of gastric carcinoma. |
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