Screening for predictive biomarkers of bevacizumab treatment in gastric cancer subcutaneous xenografts
10.3760/cma.j.issn.1671-0274.2015.02.018
- VernacularTitle:贝伐单抗治疗胃癌裸鼠皮下移植瘤的分子标志物筛选
- Author:
Qingyuan ZHANG
1
;
Jianbo XU
;
Jinning YE
;
Yujie YUAN
;
Jianhui CHEN
;
Jianjun PENG
;
Yulong HE
Author Information
1. 中山大学附属第一医院胃肠外科
- Keywords:
Stomach neoplasms;
Bevacizumab;
Biomarker;
Nude mice
- From:
Chinese Journal of Gastrointestinal Surgery
2015;(2):177-180
- CountryChina
- Language:Chinese
-
Abstract:
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) mm3 and (242.2 ±71.4) mm3 vs. (1535.2 ±625.1) mm3, 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). Conclusion VEGF and IL-8 may be used to be biomarkers candidates to predict bevacizumab effectiveness on human gastric cancer.