Effect Of Low Mloecular Weight Heparin On Tumor Growth, Metastasis And CXCR4 Expression Of Orthotopic Transplantation Gastric Tumor Model In Nude Mice

Objective: To study the effect of Low-molecular weight heparins (LMWH) on tumor growth,metastasis and the expression of cxcr4 in orthotopic transplantation gastric tumor model in nude mice.Methods: A model of human gastric cancer was established by orthotopic transplantation of histologically intact tumor tissue blocks in the gastric walls of nude mice. All mice were randomly divided into 3 groups : control group (treated with saline), LMWH group (treated with low molecular weight heparin calcium)and chemotherapy group(treated with 5-fluorouracil). Forty two days after treatment, tumor metastasis rates and tumor volume were evaluated respectively.The expressions of CXCR4 protein and mRNA were detected by immunohistochemistry and Reverse-transcription PCR (RT-PCR).Results: the tumor volume of LMWH group,chemotherapy group and the control group were 1365.00±533.82mm3,1090.95±245.42mm3,2363.85±807.61 mm3. The tumor volume of LMWH group and chemotherapy group were significantly smaller than the control group(P<0.05), there were no difference between LMWH group and chemotherapy group (P>0.05),the tumor metastasis rates were 20%, 11% and 70% in LMWH group ,chemotherapy group and the control group respectively. The tumor metastasis rates in LMWH group was significantly lower than the control group(P<0.05) ,but there were no difference between LMWH group and chemotherapy group (P>0.05). CXCR4 mRNA expression were 40%,66% and 70% in LMWH group ,chemotherapy group and the control group respectively,there were no difference among 3 groups (P>0.05) . The mRNA expression index(RI) of CXCR4 were 0.62±0.06,0.79±0.04,0.80±0.08in LMWH group ,chemotherapy group and the control group respectively, The mRNA expression (RI) of CXCR4 in LMWH group was significantly lower than the other groups(P<0.05).The case of high expression of CXCR4 protein were 2,8 and 8 in LMWH group, chemotherapy group and the control group respectively, the expression of CXCR4 protein in LMWH group was significantly lower than the other groups(P<0.05).Conclusion: Low-molecular weight heparins has inhibitory effects on tumor metastasis and tumor growth,the mechanism may involve in depressing the expression of CXCR4.