The Effect Of Rh-endostatin On Factors Associated With Vascular In Tumor And Normal Tissue

Objectives:To observe and analyze the effect of antitumor and anti-angiogenesis of rh-endostatin. To compare effect of rh-endostatin on microvasculature in tumor, myocardium and renal tissue. To investigate the mechanism of cardiovascular system's adverse effect of endostar in order to direct it's clinical application.Method:Nude mice were randomized into 4 groups, blank control group (did not burden tumor, NS 100μl·d-1), drug control group (mice not burdened tumor, rh-endostatin 400μg·d-1), model group (mice burdened tumor, NS 100μl·d-1) and treatment group (mice burdened tumor, rh-endostatin 400μg·d-1), administration was given during dl-d28. The volume of tumor and the weight of mouse were measured before and after administration. QRT-PCR assay was conducted for detecting the level of eNOS and nNOS mRNA in tumor, myocardium and kidney. The expression of CD34, MMP-2, MMP-9, HIF-la, VEGF and iNOS in tumor, myocardium and kidney were detected by immunohistochemistry. The structure of vasculature was observed by immunoenzymatic double staining with CD34 and Masson.Results:1. The results of animal experiment:The tumor volume in treatment group (48.18 mm3) is less than in the model group (113.80 mm3), the discrepancy of weight was not significant among the four groups.2. The results of Real-time PCR:After treatment of endotar, the level of eNOS and nNOS mRNA in mouse kidney significantly decreased; in myocardium the level of nNOS was decreased significantly; but the level of eNOS in myocardium and nNOS, eNOS in tumor did not change significantly.3. The results of immunohistochemistry staining:After treatment of endotar, the expression of MMP-9 and VEGF in tumor were obviously downregulated, the expression of iNOS in tumor was obviously upregulated, but the same results was not found in MMP-2, HIF-la of tumor.4. MVD of micrangium:MVD in tumor of treatment group decreased significantly compared with model group. Proportion of tumor vessels covered by collagen in treatment group increased compared with model group. However, angiogenic factors, MVD and microvasculature in myocardium and kidney did not change significantly. Conclusion:Rh-endostatin can decrease the expression of MMP-9, VEGF and MVD to inhibit growth of tumor and normalize micrangium in tumor but cannot weaken MMPs and MVD of mature micrangium in myocardium and kidney. The level of eNOS and nNOS mRNA of mouse kidney significantly decreased after treated with endotar, this maybe the reason that endostar can cause hypertension.