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In order to investigate the effect of antisense oligonucleotide (ASODN) of vascular endothelial growth factor C (VEGF-C) on lymphangiogenesis and angiogenesis of pancreatic cancer, antisense and scamble-sense oligonucleotide of VEGF-C were constructed, and the model of nude mice with orthotopically xenografted human pancreatic cancer cells (Panc-1) was established. Thirty nude mice were randomly divided into 3 groups: PBS control group (group A), scramble-sense control group (group B) and antisense group (group C). All nude mice were treated once every 2 days as 3 times per week, for 3 weeks (oligonucleotide 10 mg/kg every time). After treatments were completed, ELISA method was used to examine the concentration of VEGF-C in plasma and immunohistochemical method to examine microvessel density (MVD), lymphtic vessel density (LVD) of pancreatic cancer. The results showed that the expression of VEGF-C was inhibited significantly in group C. The concentrations were 237.5±41.5, 221.5±52.3 and 108.6±14.9 pg/mL in groups A, B and C respectively (P＜0.01). LVD in groups A, B and C was 13.8±2.1, 12.4±1.9 and 4.2±1.6 respectively (P＜0.01). MVD in groups A, B and C was 27.5±8.7, 25.9±4.2 and 19.4±5.6 respectively with no significant difference among the groups (P＞0.05). It was suggested that VEGF-C ASODN decreased the expression levels of VEGF-C in nude mice with orthotopically xenografted human pancreatic cancer, and it could inhibit lymphangiogenesis, but had no significant effect on angiogenesis.