recombinant human endostatin normalizes tumor vasculature and enhances radiation response in xenografted human nasopharyngeal carcinoma models重组人血管内皮抑制素规范化肿瘤脉管系统和提高辐射反应在人类鼻咽癌异种移植模型.pdfVIP

Recombinant Human Endostatin Normalizes Tumor Vasculature and Enhances Radiation Response in Xenografted Human Nasopharyngeal Carcinoma Models 1,2. 1,2,3. 1,2. 1,2 4 3 5 Fang Peng , Zumin Xu , Jin Wang , Yuanyuan Chen , Qiang Li , Yufang Zuo , Jing Chen , Xiao Hu1,2, Qichao Zhou1,2, Yan Wang1,2, Honglian Ma1,2, Yong Bao1,2*, Ming Chen1,2* 1 Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province, China, 2 State Key Laboratory of Oncology in South China, Guangzhou, Guangdong Province, China, 3 Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China, 4 Organ Transplantation Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China, 5 Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong Province, China Abstract Background: Hypoxic tumor cells can reduce the efficacy of radiation. Antiangiogenic therapy may transiently ‘‘normalize’’ the tumor vasculature to make it more efficient for oxygen delivery. The aim of this study is to investigate whether the recombinant human endostatin (endostar) can create a ‘‘vascular normalization window’’ to alleviate hypoxia and enhance the inhibitory effects of radiation therapy in human nasopharyngeal carcinoma (NPC) in mice. Methodology/Principal Findings: Transient changes in morphology of tumor vasculature and hypoxic tumor cell fraction in response to endostar were detected in mice bearing CNE-2 and 5–8F human NPC xenografts. Various treatment schedules were tested to assess the influence of endostar on the effect of radiation therapy. Several important factors relevant to the angiogenesis were identified through immunohisto