Zhang Qingyuan, Xu Jianbo, Ye Jinning, Yuan Yujie, Chen Jianhui, Peng Jianjun, He Yulong
Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Zhonghua Wei Chang Wai Ke Za Zhi. 2015 Feb;18(2):177-80.
To establish subcutaneous xenograft models of gastric cancer in nude mice and to screen the predictive biomarkers of bevacizumab effectiveness.
Subcutaneous xenograft models were established using BGC823 gastric cancer cell line in 20 male 4-week old BALB/C-nu/nu nude mice and were randomly divided into four groups, bevacizumab group(15 mg/kg), 5-FU group(15 mg/kg), combined group and control group, with 5 mice in each group. Bevacizumab and 5-FU were administered intraperitoneally every other day for three weeks. After treatment, tumor size and inhibition rate were calculated. Expression of CD31 was examined by immunohistochemistry for evaluation of microvascular density(MVD). Levels of human vascular endothelial growth factor(VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PIGF) and interleukin 8(IL-8) were tested by enzyme linked immunosorbent assay(ELISA).
Compared to the control group, bevacizumab group and combined group had a significantly lower MVD(5.2±1.0 and 4.3±1.2 vs. 13.8±1.6, P<0.05), a smaller tumor volume [(305.6±184.1) mm(3) and (242.2±71.4) mm(3) vs.(1535.2±625.1) mm(3), P<0.05], and lower levels of VEGF and IL-8 in tumor tissues [VEGF:(351.6±84.1) ng/L and (242.2±71.4) ng/L vs. (1256.7±702.1) ng/L, P<0.05); IL-8:(20 903±1485) ng/L and (27 489±6772) ng/L vs. (57 032±2437) ng/L, P<0.05]. The above parameters were not significantly different between 5-FU group and control group(all P>0.05). Levels of bFGF and IGF were not significantly different among four groups as well(all P>0.05).
VEGF and IL-8 may be used to be biomarkers candidates to predict bevacizumab effectiveness on human gastric cancer.
建立裸鼠胃癌皮下移植瘤模型并筛选贝伐单抗疗效的预测生物标志物。
采用BGC823胃癌细胞系在20只4周龄雄性BALB/C-nu/nu裸鼠中建立皮下移植瘤模型，随机分为四组，即贝伐单抗组（15 mg/kg）、5-氟尿嘧啶组（15 mg/kg）、联合组和对照组，每组5只。贝伐单抗和5-氟尿嘧啶每隔一天腹腔注射给药，共三周。治疗后，计算肿瘤大小和抑制率。通过免疫组织化学检测CD31的表达以评估微血管密度（MVD）。采用酶联免疫吸附测定（ELISA）检测人血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）、胎盘生长因子（PIGF）和白细胞介素8（IL-8）的水平。
与对照组相比，贝伐单抗组和联合组的MVD显著降低（5.2±1.0和4.3±1.2 vs. 13.8±1.6，P<0.05），肿瘤体积更小[（305.6±184.1）mm³和（242.2±71.4）mm³ vs.（1535.2±625.1）mm³，P<0.05]，肿瘤组织中VEGF和IL-8水平更低[VEGF：（351.6±84.1）ng/L和（242.2±71.4）ng/L vs.（1256.7±702.1）ng/L，P<0.05；IL-8：（20 903±1485）ng/L和（27 489±6772）ng/L vs.（57 032±2437）ng/L，P<0.05]。5-氟尿嘧啶组与对照组上述参数无显著差异（均P>0.05）。四组之间bFGF和IGF水平也无显著差异（均P>0.05）。
VEGF和IL-8可作为预测贝伐单抗对人胃癌疗效的生物标志物候选物。
