Zhu Yifan, Tibensky Igor, Schmidt Jan, Hackert Thilo, Ryschich Eduard, Jäger Dirk, Büchler Markus W, Märten Angela
Department of Surgery, National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
J Immunother. 2008 Jan;31(1):28-33. doi: 10.1097/CJI.0b013e318157c682.
There are clinical data showing encouraging results for combining chemoradiotherapy with interferon (IFN)-alpha (CapRI scheme) for the treatment of pancreatic carcinoma. Here, it was tried to evaluate the antiangiogenic effect of IFN-alpha in combination with chemotherapy. Mice were inoculated with syngeneic pancreatic carcinoma cells in the pancreas. After 5 days, the animals were treated with 5-fluorouracil (5-FU)+/-IFN-alpha. Tumor growth, vascular endothelial growth factor (VEGF) serum levels and VEGF-R expression, real-time reverse transcription-polymerase chain reaction of mRNA coding for RGS-5, an angiogenic pericyte marker at sites of physiologic and pathologic angiogenesis and impact of IFN-alpha treatment on vessel density by CD31 stain and intravital microscopy were analyzed. The addition of IFN-alpha to 5-FU-treatment decreased tumor volume, reduced serum level of VEGF, and down-regulated the expression of VEGF-receptor significantly. Furthermore, the combination therapy revealed a decrease in vessel density and a down-regulation of RGS-5, which is a protein involved in angiogenic tumor vasculature. IFN-alpha significantly improves the outcome of 5-FU-therapy in treating pancreatic carcinoma. This is at least partly mediated by IFN-alpha antiangiogenic properties, which acts along with 5-FU on the VEGF system, vessel density, and RGS-5 expression in pericytes.
有临床数据表明，化疗放疗联合α干扰素（IFN-α）（CapRI方案）治疗胰腺癌的效果令人鼓舞。在此，我们试图评估α干扰素联合化疗的抗血管生成作用。将同基因胰腺癌细胞接种到小鼠胰腺中。5天后，用5-氟尿嘧啶（5-FU）±α干扰素对动物进行治疗。分析肿瘤生长、血管内皮生长因子（VEGF）血清水平和VEGF-R表达、编码RGS-5（一种在生理和病理血管生成部位的血管生成周细胞标志物）的mRNA的实时逆转录聚合酶链反应，以及α干扰素治疗对通过CD31染色和活体显微镜观察的血管密度的影响。在5-FU治疗中添加α干扰素可减小肿瘤体积、降低VEGF血清水平，并显著下调VEGF受体的表达。此外，联合治疗显示血管密度降低，RGS-5下调，RGS-5是一种参与肿瘤血管生成的蛋白质。α干扰素显著改善5-FU治疗胰腺癌的效果。这至少部分是由α干扰素的抗血管生成特性介导的，它与5-FU共同作用于VEGF系统、血管密度和周细胞中的RGS-5表达。
