The Experimental Study On Effect Of Sodium Cantharidinate Injection On The Lymphangiogenic Growth Factors Of Nude Mice With Human Gastric Carcinoma

Objective:To observe the effects of growth and lymph angiogenesis on BALB/C nude mice with transplanted human gastric carcinoma cell NUGC-4acted by Sodium antharidinate Injection. To explore the mechanism of Sodium Cantharidinate Injection in inhibiting lymphatic metastasis of gastric carcinoma by studying its effects on the expression of vascular endothelial growth factor-C(VEGF-C) and vascular endothelial growth factor receptor-3(VEGFR-3) in the transplanted tumor tissue.Methods:Through the method of surgical orthotopic implantation to set up the gastric cancer model in BALB/C nude mice by using the red fluorescent protein (RFP) transfected human gastric carcinoma NUGC-4cells.32NUGC-4-RFP nude mice were randomly divided into4groups:Sodium Cantharidinate large dose group, Sodium Cantharidinate low dose group,5-Fu group, and normal saline group.9days after the surgery, the nude mice were treated with Sodium Cantharidinate large dose, Sodium Cantharidinate low dose,5-Fu and normal saline.At the end of the experiment, all mice were sacrificed and open fluorescent images of tumors and metastasis expressing RFP were acquired, and the tumor was removed from the nude mice, the tumors were weighted, tumor inhibition rate and lymph node metastasis rate were calculated.The expressions of VEGF-C、VEGFR-3in the tumor tissue were detected and the lymphatic microvessel density (LMVD) in tumor was counted and analyzed Semi-quantitatively by immunohistochemisty.Results:1. All groups of the orthotopic transplantation tumors in the nude mice were grew well, and some of them with lymphatic metastasis. Lymph node metastasis rates of Sodium Cantharidinate large dose group、Sodium Cantharidinate low dose group、5-Fu group and normal saline group were37.5%、75%、50%and87.5%。2. Compared with normal saline group, average tumor weight of Sodium Cantharidinate large dose group and5-Fu group were lower (P<0.05);compared with Sodium Cantharidinate large dose group,5-Fu group had no significant difference (P>0.05).Comparing the average tumor weight, there was no significant difference between Sodium Cantharidinate low dose group and normal saline (P>0.05)3. Compared with normal saline group, the expressions of VEGF-C、VEGFR-3proteins as well as LMVD in Sodium Cantharidinate large dose group、Sodium Cantharidinate low dose group and5-Fu group were decreased, the difference had a statistical significance (P<0.05) Compared with Sodium Cantharidinate large dose group,5-Fu group had no significant difference (P>0.05). Compared with Sodium Cantharidinate low dose group, the expressions of VEGF-C、VEGFR-3proteins in large dose group was obviously decreased, the difference had a statistical significance (P<0.05)Conclusion:1. Sodium Cantharidinate large dose group can obviously inhibit the tumor growth and lymphatic metastasis of the orthotopic transplantation model of human gastric carcinoma NUGC-4in nude mice.2. Sodium Cantharidinate can down-regulate the expressions of VEGF-C、VEGFR-3proteins in the tumor tissue, which may be the mechanism of Sodium Cantharidinate in inhibiting lymphatic metastasis of gastric carcinoma.