摘要
目的：通过胃癌的裸鼠皮下移植瘤模型筛选出能够预测贝伐单抗疗效的分子标志物。方法选择4周龄雄性BALB／C-nu／nu裸鼠20只，制备人胃癌细胞BGC823皮下移植瘤模型，随机分为对照组、氟尿嘧啶（5-FU）组（5-FU组，15 mg／kg）、贝伐单抗组（BVZ组，15 mg／kg）和联合治疗组（贝伐单抗联合5-FU），每组各5只。隔日腹腔注射给药，连续3周。治疗结束时，计算肿瘤大小和抑瘤率；采用免疫组织化学方法检测肿瘤内CD31的表达情况以计数微血管密度（MVD）；采用酶联免疫吸附法检测裸鼠肿瘤组织中血管内皮生长因子（VEGF）、人碱性成纤维细胞因子（bFGF）、人胎盘生长因子（PIGF）和人白介素8（IL-8）的表达情况。结果与对照组相比，治疗结束时BVZ组和联合给药组肿瘤MVD下降（5．2±1．0和4．3±1．2比13．8±1．6，P＜0．05），肿瘤体积缩小[（305．6±184．1） mm^3和（242．2±71．4） mm^3比（1535．2±625．1） mm^3，P＜0．05），肿瘤组织中 VEGF[（351．6±84．1） ng／L和（242．2±71．4） ng／L比（1256．7±702．1） ng／L，P＜0．05）和IL-8[（20903±1485） ng／L和（27489±6772） ng／L比（57032±2437） ng／L，P＜0．05）表达水平下降；而5-FU组与对照组上述指标的差异均无统计学意义（均P＞0．05），bFGF和PIGF在各组间表达水平的差异均无统计学意义（均P＞0．05）。结论 VEGF和IL-8可能成为预测贝伐单抗疗效的分子标志物。
Objective To establish subcutaneous xenograft models of gastric cancer in nude mice and to screen the predictive biomarkers of bevacizumab effectiveness. Methods 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）. Results 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＆amp;nbsp;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）. Conclusion VEGF and IL-8 may be used to be biomarkers candidates to predict bevacizumab effectiveness on human gastric cancer.
出处
《中华胃肠外科杂志》
CAS
CSCD
北大核心
2015年第2期177-180,共4页
Chinese Journal of Gastrointestinal Surgery
基金
广东省科技计划项目（20128060300011）
关键词
胃肿瘤
贝伐单抗
分子标志物
裸鼠
Stomach neoplasms
Bevacizumab
Biomarker
Nude mice
