Abstract: Objective To investigate the effect of vascular endothelial growth factor(VEGF) antisense oligonucleotides(ASODN) or/and low molecular weight heparin(LMWH) fragmin on tumor growth,coagulation,thrombosis and embolism in mice Lewis lung cancer.Methods 40 mice with Lewis lung cancer were randomly divided into five groups: control group,VEGF-ASODN group,VEGF mismatch sense oligonucleotides(MSODN) group,LMWH group,and combined group.Sodium chloride,VEGF-ASODN,VEGF-MSODN,fragmin,and VEGF-ASODN plus fragmin were given respectively(once every two days,15 times altogether).Volume and weight of subcutaneous tumors were measured;Microvessel density(MVD) in tumor mass was measured by imuunohistochemistry staining;Concentration of plasma VEGF and coagulation initiator tissue factor(TF) were detected by ELASA method;thrombosis and embolism were detected by tissue HE staining method;VEGF and TF protein level in tumor tissue were detected by Western blot assay.Results Tumor growth inhibitory rates of ASODN group,LMWH group,and combined group were 47.34%,27.31% and 59.03%,respectively.There was significant difference on tumor growth inhibitory rates and MVD between above three treated groups and control group as well as MSODN group(P<0.05).Mean concentration of plasma VEGF in ASODN group,combined group were(9.66±(1.02))ng/L,(9.39±2.26)ng/L which were lower than that of control group [(14.39±3.76)ng/L](P<0.05);Mean concentrationof plasma TF in LMWH(group,) combined group were((20.00)±(1.26))ng/L,((23.50)±(5.62))ng/L which were lower than that of control group [(27.08±5.40)ng/L](P<0.05).Pulmonary thromboembolism(PTE) was relatively common,rates of PTE in control group,ASODN group,MSODN group,LMWH group,combined group were 37.5%,50.0%,37.5%,25.0%,25.0%,respectively. In ASODN group,VEGF protein expression was lower,but TF protein expression was higher.Conclusion VEGF-ASODN combined with LMWH can enhance anti-tumor effect.VEGF-ASODN may exacerbate hypercoagulation so as that the risk to PTE increased.However LMWH may reduce the tendency of hypercoagulation.

Key words: vascular endothelial growth factor, low molecular weight heparin, lung neoplasm, pulmonary thromboembolism