Investigation of the novel anti-angiogenesis therapy in an orthotopic implantation mouse model of human malignant pleural mesothelioma cells

采用人恶性胸膜间皮瘤细胞原位移植小鼠模型，观察其对抗血管内皮生长因子治疗的抵抗力。抗血管内皮生长因子治疗早期肿瘤血管生成受到抑制，但治疗后期微血管密度增加，提示肿瘤对抗血管内皮生长因子治疗产生了抵抗力。我们发现宿主FGF2在耐药肿瘤中表达上调，联合抗FGFR治疗比单独使用抗血管内皮生长因子治疗更有效。血管生成转换成不同的因子，如FGF2，似乎在抗血管内皮生长因子治疗的抵抗中起重要作用。

The resistance against anti-VEGF therapy was investigated using orthotopic implantation mouse model of human malignant pleural mesothelioma cells. Although tumor angiogenesis was inhibited in the early phase ofanti-VEGF therapy, microvessel density was turned to increase in the late phase ofthe therapy, suggesting that the tumor acquired the resistance against anti-VEGF therapy. We found that the host FGF2 was up-regulated in the resistant tumor, and anti-FGFR therapy in combination with anti-VEGF therapy was more effective compared to anti-VEGF therapy alone. Angiogenic switch into different factors such as FGF2 seemed to play important role in the resistance against anti-VEGF therapy.