Effect of antisense oligodeoxynucleotide of vascular endothelial growth factor C on lymphangiogenesis and angiogenesis of pancreatic cancer.
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.
Li
Kai
K
Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. tj918@163.com
Tao
Jing
J
Li
Tao
T
Yu
Zhou
Z
Yang
Zhiyong
Z
Wu
Heshui
H
Xiong
Jiongxin
J
Wang
Chunyou
C
D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005169:Factor VIII / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D007150:Immunohistochemistry; D042583:Lymphangiogenesis / Q000187:drug effects*; D051379:Mice; D008833:Microcirculation / Q000187:drug effects / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000098:blood supply*; D011897:Random Allocation; D042582:Vascular Endothelial Growth Factor C / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D016376:Oligonucleotides, Antisense; D042582:Vascular Endothelial Growth Factor C; D005169:Factor VIII; D040321:Vascular Endothelial Growth Factor Receptor-3