Lung metastases of colorectal cancer boosted by bevacizumab in mice and possible mechanism / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To investigate the effect of bevacizumab ,an anti-human vascular endothelial growth factor monoclonal antibody,on pulmonary dissemination of colorectal cancer. METHODS A metastatic colorectal cancer mouse model was established. Mice were randomly divided into two groups(n=8). The mice in experimental group were administered ip with bevacizumab at the dosage of 5 mg · kg-1,and those in control group were given isotype IgG at the same dosage. The antibodies were administered on 2 d before initiation of model establishment and 2 d after that,then once every 5 d for 4 weeks,for a total of 7 times. Liver and lung metastases were determined by histopathological examination. The chemokine receptor C-X-C receptor 4(CXCR4)and its ligand C-X-C ligand 12(CXCL12)mRNA expression in the lung were detected by quantitative RT-PCR. Human colon cancer cells HCT116 were treated with bevacizumab(5 mg·L-1)for 24 h. The expression levels of vascular endothelial growth factor receptor 1(VEGFR1)and CXCR4/7 protein as well as CXCR3/4/7 mRNA were examined by Western blotting and quantitative RT-PCR respectively. RESULTS The number of mice(2/8) with liver metastases was reduced,while the number of mice(8/8) with lung metastases increased in experimental group compared with isotype IgG-treated group(6/8 and 2/8 respectively,P<0.05). The mRNA expression level of CXCR4 and CXCL12 in lung tissue was significantly up-regulated in bevacizumab-treated group com?pared with control group(P<0.05). The mRNA and protein expression level of CXCR4 and CXCR7 was dramatically increased in HCT116 cells treated with bevacizumab(P<0.05). CONCLUSION Bevacizumab can potentially promote lung metastases of colorectal cancer,which may be related to up-regulation of CXCR4 and CXCL12 expression.