The Effect Of Panaxoside-Rg3 In The Treatment On Malignant Ascites In Mice

Objective: We observe the effect of panaxoside-Rg3 on mice implanted intraperitoneally with ascitogenous tumor cells of H22 lines. To establish an experimental malignant ascites tumor model in mice, investigate its mechanism in blood vessel endothelium growth factor(VEGF)and microvessel density(MVD)level. We determined whether panaxoside-Rg3 could potentiate the anti-tumor effect of cisplatin(DDP) on the formation of malignant ascites.Methods: 48 female and 48 male Kunming mice were randomized into six groups: GroupⅠ,normal saline as control group(0．9%NS); GroupⅡ,cisplatin as positive group(DDP 0．5mg/kg); GroupⅢ,low-dose panaxoside-Rg3(LPD 0．3mg/kg); GroupⅣ, middle-dose panaxoside-Rg3 (MPD 1．0mg/kg); GroupⅤ,high-dose panaxoside-Rg3(HPD 3．0mg/kg); GroupⅥ, combination Production(MPD 1．0mg/kg + DDP 0．5mg/kg). All groups were inoculated with ascites tumor cells of H22 lines, 24 hours later intraperitoneal infusion 0．2ml medicines was given once every day for 14 days..At the same time, We observed animation and body weight. 24 hours after the over of the treatment, half mice of each group were executed. Production of ascites,number of tumor cells in ascites and survival rate of tumor cells, formation rate of peritoneum tumor nodal were observed respectively. Morphological of tumor cell in abdominal cavity and new vascular in peritoneum tumor node were observed by transmission electron microscope. The VEGF levels in the ascites and the serum were measured and expressions of MVD of peritoneum tumor node were observed. Others were observed the survival.Results: 1 .Panaxoside-Rg3 inhibited the production of ascites. (1) The time of emerging ascites of groupⅡ-Ⅴpostponed obviously than groupⅠ. Production of ascites (P<0．0033) ,number of tumor cells and survival rate of tumor cells of group Ⅱ-Ⅴdescended than groupⅠ, formation rate of peritoneum tumor nodal in combination production group was descended than groupⅠ(P<0．05) . (2) Number of tumor cells and survival rate of tumor cells of the HPD group were significantly lower than the DDP groups(P < 0．05) . (3) With the increase of concentration of panaxoside-Rg3, number of tumor cells and survival rate of tumor cells in ascites dropped(P<0．05) . Number of tumor cells and survival rate of tumor cells in ascites of the combination group were lower than all concentration groups of panaxoside-Rg3(P<0．05) . (4) The time of emerging ascites of groupⅥpostponed obviously than groupⅠ. Production of ascites (P<0．0033) ,number of tumor cells and survival rate of tu mor cells of groupⅥdescended than groupⅠ, formation rate of peritoneum tumor nodal of groupⅥwas descended than groupⅠ(P<0．05) . Number of tumor cells and survival rate of tumor cells of groupⅥwere significantly lower than the DDP groups(P<0．05) . Production of ascites was reduced than the LPD group(P<0．0033) .2．Angiogenesis inhibitor panaxoside-Rg3 effected on the survival period of tumor-loading mice:GroupⅡ-Ⅵobviously prolonged life of mice. The combination group was the most outstanding however were not significantly different from those of the MPD group(P>0．05) .3．The mechanism that panaxoside-Rg3 inhibited the production of ascites was th-ese: (1) Enzyme linked immunosorbent assay(ELISA) method is used to detect the di-fferent VEGF level in the ascites and serum of all groups. With the increase of conce-ntration of panaxoside-Rg3,The VEGF levels of the ascites and the serum dropped(P <0．05) ,and were descended than the NS group and the DDP group(P<0．05) .Expre-ssions of microvessel dense in peritoneum of NS group and DDP group were signific-antly different from those of various concentration of panaxoside-Rg3 and combina-tion by immunohistochemical staining with CD31 antibody(P<0．05) . (2) Morpholo-gical changes of tumor cells in panaxoside-Rg3 group were observed with electromic-roscope, more apoptosis and necrosis cells appeared. Capillary vessel basal lamina was smoothing,integrated and thickness at equal pace,breakage or famine was not bee-n observed.Conclusion: 1．Both angiogenesis inhibitor panaxoside-Rg3 and DDP inhibit the formation of malignant ascites in mice, furthermore, Middle-dose panaxoside-Rg3 gro -up and DDP group have fairly therapeutic effect; With the increase of concentration of panaxoside-Rg3, inhibitory action of the production of malignant ascites enhanced.2．Angiogenesis inhibitor panaxoside-Rg3 decreases the permeability of micrangium and inhibit the neovascularization of peritoneum by decreasing the VEGF and MVD level, accordingly, panaxoside-Rg3 inhibit the formation of malignant ascites.3．The combination of panaxoside-Rg3 and DDP might produce additive effect on the formation of malignant ascites.4．The reserch would offer foundation of theory for clinical application.