Wang Ning, Wang Bin, Wang Ya-Jie
Department of Oncology, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, P. R. China.
Ai Zheng. 2006 Sep;25(9):1076-81.
BACKGROUND & OBJECTIVE: The failure to treat gastric cancer is often due to the recurrence or dismal metastasis of cancer and the poor response to traditional chemotherapeutic or radiotherapeutic regimens. Vascular endothelial growth factor (VEGF) is related closely to the growth and metastasis of gastric cancer. This study was to examine the effects of Avastin, a monoclonal antibody developed against VEGF, with or without 5-fluorouracil (5-FU) on the growth, metastasis, and angiogenesis of a gastric cancer model.
A metastasis model of human gastric cancer was established by orthotopic transplantation of histologically intact human tumor tissue blocks in the gastric walls of nude mice. All mice were randomly divided into 4 groups: control group, 5-FU group, Avastin group, and combination treatment group. Forty-two days after treatment, tumor weight, inhibition rates, intratumoral microvessel density, apoptosis index, and presence of metastasis were evaluated.
Combination therapy with 5-FU and Avastin augmented the reduction of primary tumor growth and inhibited metastasis compared with treatment with either agent alone. After treatment with Avastin plus 5-FU, a significant increase in apoptotic tumor cells and a decrease in microvessel density were observed.
Avastin plus 5-FU can induce apoptosis in gastric cancer cells and has strong inhibitory effects on tumor growth and the metastasis to the liver. Anti-VEGF therapy in combination with traditional chemotherapy may be a novel therapeutic approach for advanced gastric cancer.
胃癌治疗失败往往是由于癌症复发或远处转移以及对传统化疗或放疗方案反应不佳。血管内皮生长因子（VEGF）与胃癌的生长和转移密切相关。本研究旨在探讨抗VEGF单克隆抗体阿瓦斯汀联合或不联合5-氟尿嘧啶（5-FU）对胃癌模型生长、转移及血管生成的影响。
通过将组织学完整的人肿瘤组织块原位移植到裸鼠胃壁建立人胃癌转移模型。所有小鼠随机分为4组：对照组、5-FU组、阿瓦斯汀组和联合治疗组。治疗42天后，评估肿瘤重量、抑制率、瘤内微血管密度、凋亡指数及转移情况。
与单独使用任一药物治疗相比，5-FU与阿瓦斯汀联合治疗可增强对原发肿瘤生长的抑制并抑制转移。阿瓦斯汀加5-FU治疗后，观察到凋亡肿瘤细胞显著增加，微血管密度降低。
阿瓦斯汀加5-FU可诱导胃癌细胞凋亡，对肿瘤生长及肝转移具有强烈抑制作用。抗VEGF治疗联合传统化疗可能是晚期胃癌的一种新治疗方法。
