Effect of bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor, on peritoneal metastasis of MNK-45P human gastric cancer in mice.

BACKGROUND: The aim of this study was to clarify the effect of bevacizumab on gastric cancer with peritoneal metastasis in nude mice.

MATERIALS AND METHODS: The expression of vascular endothelial growth factor mRNA (VEGF mRNA) in four gastric cancer cell lines, NCI-N87, MKN-45, MKN-45P, and Kato-III, was examined by polymerase chain reaction. We created a model of peritoneal metastasis by injecting mice with the human gastric cancer cell line MKN-45P. Mice were injected intraperitoneally with bevacizumab (0.1 mg/100 microL) on days 5-14, after inoculation (n = 10) or with phosphate-buffered saline (PBS) over the same time period (n = 10). The maximum abdominal circumference, ascites volume, and the total number and weight of peritoneal tumors were measured. To assess the effect of bevacizumab on angiogenesis, immunohistochemical analysis was performed.

RESULTS: VEGF mRNA was expressed at a high level in MKN-45P cells as well as MKN-45 and Kato-III. The mean maximum abdominal circumference and ascites volume in the bevacizumab group were significantly less than those in the control group (P < 0.001, respectively). The total weight of disseminated tumors in the bevacizumab group was also significantly less than that in the control group (P < 0.01). In addition, immunohistochemical analysis of CD31-stained peritoneally disseminated nodules showed that the vessel area in the bevacizumab group was significantly less than that in the control group (P < 0.001).

CONCLUSIONS: These results show that intraperitoneal administration of bevacizumab inhibits peritoneal metastasis and reduces malignant ascites in tumor-bearing mice.