Avastin对胃癌裸鼠原位移植模型血管生成的影响

背景与目的:血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)和肿瘤的生长和转移密切相关,本实验通过VEGF单克隆抗体Avastin联合或不联合氟尿嘧啶(5-fluorouracil,5-FU),对人类胃癌裸鼠原位种植模型的肿瘤生长和转移进行干预治疗,从而探讨Avastin对胃癌生长、转移和血管生成的抑制作用。方法:应用原位移植方法建立裸鼠胃癌转移模型,术后10天将裸鼠随机分为4组:对照组、5-FU单药组、Avastin单药组和联合用药组。经过6周的治疗,对裸鼠原位肿瘤的瘤重、抑瘤率、肿瘤微血管密度、凋亡指数以及肝脏转移灶进行检测和分析。结果:和对照组相比,5-FU单药组、Avastin单药组和联合用药组原位移植肿瘤重量明显降低,抑瘤率分别为37.52%,58.76%和98.51%。微血管密度Avastin单药组和联合用药组均比对照组明显减少(8.40±1.26和7.20±1.23vs15.30±1.06),而5-FU组与对照组之间没有显著的差别;Avastin单药组和联合用药组的凋亡指数比对照组明显升高[(11.50±1.58)%和(13.60±1.35)%vs(4.70±1.70)%]。联合应用Avastin和5-FU对肝脏转移灶具有明显的抑制作用,而其他3组的抑制肝转移效果没有明显的差别。结论:抗VEGF抗体Avastin通过抑制肿瘤新生血管的生成而诱导胃癌细胞凋亡,进而显著抑制裸鼠原位肿瘤的生长。联合应用Avastin和5-FU不仅对原位肿瘤的生长抑制最为明显,而且对肝脏转移有显著的抑制作用。因此,联合应用Avastin和传统的细胞毒化疗药物对胃癌的治疗效果更显著。

Effect of vascular endothelial growth factor antibody Avastin on angiogenesis of human gastric cancer growing orthotopically in nude mice

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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.