[Effects of VEGF-A/VEGF-C antisense oligodeoxynucleotide on angiogenesis, lymphangiogenesis, and tumor growth of breast cancer].
OBJECTIVE
Angiogenesis and lymphangiogenesis are closely related to tumor metastasis. Vascular endothelial growth factor-A (VEGF-A) is considered as an important factor in promoting angiogenesisû while VEGF-C is the most critical factor in VEGF family in promoting lymphangiogenesis, and exerts synergistic effect with VEGF-A in angiogenesis. This study was to investigate the effects of VEGF-A/VEGF-C antisense oligodeoxynucleotide (ASODN) on the angiogenesis, lymphangiogenesis, and tumor growth of breast cancer.


METHODS
VEGF-A/VEGF-C ASODN was constructed and injected into orthotopic transplantation tumor model of human breast cancer in athymic mice. Tumor growth was observed. The expression of VEGF-A and VEGF-C was detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Microvessel density (MVD) and lymphatic microvessel density (LMVD) were measured by enzymohistochemistry.


RESULTS
Tumor formation time was significantly longer and tumor weight was significantly lower in ASODN group than in control group [(13.00+/-2.83) days vs. (7.67+/-1.63) days, P<0.05û (0.45+/-0.14) g vs. (0.92+/-0.37) g, P<0.05]. The inhibition rate of tumor growth was 51.09% in ASODN group. The mRNA and protein expression of VEGF-A and VEGF-C were significantly weaker in ASODN group than in control group (P<0.05) The MVD and LMVD was significantly lower in ASODN group than in control group (21.83+/-2.86 vs. 41.33+/-4.03, 18.67+/-4.67 vs. 31.83+/-2.33, P<0.05).


CONCLUSIONS
VEGF-A/VEGF-C ASODN could inhibit angiogenesis and lymphangiogenesis in breast cancer, and further inhibit tumor growth and metastasis.
Chen
Ji-Shan
JS
Department of Pathology, Guangzhou Medical College, Guangzhou, Guangdong, 510182, PR China.
Zhang
Ya-Jie
YJ
Hu
Shuai-Er
SE
Zhang
Hui-Qiu
HQ
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D042583:Lymphangiogenesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000473:pathology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis* / Q000235:genetics
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C