| Background and Purpose The mortality rate of gastric cancer ranks the second in all the malignant tumors around the world, and it's the most common gastrointestinal tumors in our country.Since the high rate of recurrence and metastasis after surgeries, so the comprehensive treatment is the main treatment for the gastric cancer. In recent years, molecular targeted therapy has become the research focus in the field of anti-tumor. Neuropili n-1 as a multifunctional receptor to participate in the signal transduction of various cytokines, such as VEGF, PDGF, b FGF, etc, to promote tumor angiogenesis. Many clinical studies showed that monoclonal antibody targeting NRP-1 has good antitumor efficacy. Through the drug delivery mode of small dose and high frequency, some chemotherapy drugs have the effect of anti- tumor angiogenesis, and this method of therapy was called metronomic chemotherapy in clinic. Docetaxel has become a first-line therapeutic drug for gastric cancer from 2006, and the researches about metronomic chemotherapy of docetaxel in gastric cancer increasing day by day.This article aim at observing the antitumor efficacy of NRP-1 monoclonal antibody(NRP-1m Ab) in combination with metronomic chemotherapy(MCT) with docetaxel in BALB/c nude mice gastric cancer model and preliminarily investigate its possible mechanism of the treatment of gastric cancer. To provide experimental basis of developing a new type treatment for gastric cancer.Methods BGC-823 gastric cancer cells were injected subcutaneously into BALB/c nude mice. BALB/c nude mice were randomised into control group, Maximum tolerated dose( MTD) group, NRP-1m Ab group, MCT group and combination group.According therapy was given to different groups. The general condition of mice was observed. Mice weight and tumor diameter were measured every other day. Venous blood samples were collected before treatment, in the middle of treatment and before death, respectively. Then tumors were weighed after killing the mice. The histological appearance of tumor tissue were observed by HE staining and NRP-1 protein expression were detected in tumor tissues of mice by immunohistochemistry.Results The survival rate of subcutaneously transplanted tumor model was 100%.Compared to control group and other groups, the tumor growth curve in combination group was near flat and mice in that group had no obvious toxic side effects. At the end of experiment, the weights of tumor in control group, MTD group, NRP-1m Ab group, MCT group and combination group were(1.247±0.494)g,(0.817±0.163)g,(0.867±0.361)g,(0.748±0.152)g,(0.394±0.128)g, respectively. The tumor growth inhibition rates were 34.47% for MTD group, 30.43%for NRP-1m Ab group,40.01% for MCT group and 68.39% for combination group respectively. The results by HE staining showed that the tumor vessels of control group were remarkably higher than that of the other four experiment groups. The results by immunohistochemistry showed that the expression of NRP-1 in tumor tissues of control group was remarkably higher than that of the other four experiment groups.Which, the combination group was minimum.Conclusion NRP-1m Ab in combination with metronomic chemotherapy with docetaxel synergistically inhibit the tumor growth and metastasis in mouse BGC-823 gastric cancer model without increasing toxic and side effects. One of the possible mechanisms is to implement anti tumor indirectly by down-regulating NRP-1 protein expression of mouse tumor tissues. |
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