[Effects of VEGF-A/VEGF-C antisense oligodeoxynucleotide on angiogenesis, lymphangiogenesis, and tumor growth of breast cancer]

BACKGROUND & 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).

CONCLUSION: VEGF-A/VEGF-C ASODN could inhibit angiogenesis and lymphangiogenesis in breast cancer, and further inhibit tumor growth and metastasis.