Dual blockade of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2) exhibits potent anti-angiogenic effects

作者：Li, Dong; Xie, Kun; Zhang, Longzhen; Yao, Xuejing; Li, Hongwen; Xu, Qiaoyu; Wang, Xin; Jiang, Jing; Fang, Jianmin^*

来源：Cancer Letters, 2016, 377(2): 164-173.

DOI：10.1016/j.canlet.2016.04.036

• VEGF
• FGF-2
• Dual decoy receptor
• Angiogenesis
• Anti-angiogenic therapy
• Cancer therapy

Both vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF or FGF-2) are potent pro-angiogenic factors and play a critical role in cancer development and progression. Clinical anti-VEGF therapy trials had a major challenge due to upregulated expression of other pro-angiogenic factor, like FGF-2. This study developed a novel chimeric decoy receptor VF-Trap fusion protein to simultaneously block activity of both VEGF and FGF pathways in order to achieve an additive or synergistic anti-tumor effect. Our in vitro data showed that VF-Trap potently blocked proliferation and migration of both VEGF-and FGF-2-induced vascular endothelial cells. In animal models, treatment of xenograft tumors with VF-Trap resulted in significant inhibition of tumor growth compared to blockage of the single molecule, like VEGF or FGF blocker. In addition, VF-Trap was also more potent in inhibition of ocular angiogenesis in a mouse oxygen-induced retinopathy (OIR) model. These data demonstrated the potent anti-angiogenic effects of this novel VF-Trap fusion protein on blockage of VEGF and FGF-2 activity in vitro and in animal models. Further study will assess its effects in clinic as a therapeutic agent for angiogenesisrelated disorders, such as cancer and ocular vascular diseases.

• 出版日期2016-7-28
• 单位四川大学; 同济大学