Short interfering RNA vectors against VEGF-C and VEGF-A suppress lymphatic metastasis and lymphatic metastasis of mammary cancer model

点击翻译按钮获取中文摘要

Human breast cancers metastasize mainly to the lymph nodes, lungs, and intractable metastasis leads to death. VEGF-C expression has been shown to correlate with lymph node metastasis in a variety of human cancers. VEGF-A has also been reported to participate on hematogeneous metastasis. Syngeneic inoculated metastatic mammary cancers received direct intratumoral injection of psiRNA-SCR control vector, psiRNA-VEGF-C vector, psiRNA-VEGF-A or their combination once a week for 8 weeks. We applied electrogene transfer to the tumors after each injection. Tumor volume was significantly lower in the psiRNA-VEGF-A and the combination groups as compared to the control group. Both incidence and multiplicity of the lymph node metastasis were significantly less frequent in all therapeutic groups. While incidence of the lung metastasis in all groups was similar, the number of lung metastatic foci was significantly decreased in the combination group only. In addition, the numbers of dilated lymphatic vessels containing intaluminal tumor cells were significantly decreased in all therapeutic groups. Our data suggest that not only VEGF-C but also VEGF-A correlate to lymphatic metastasis, and the observed anti-metastasis activity of siRNA against VEGF-C and VEGF-A may be of high clinical significance in the treatment of metastatic breast cancer.