OBJECTIVETo compare the effect of rh-endostatin on micrangium in tumor and myocardial tissue in nude mice.

METHODSNude mice were randomized into 4 groups (10 mice in each group), blank control group (without tumor burden, received NS 100 µl×d(-1) injection), drug control group (without tumor burden, received rh-endostatin 400 µg×d(-1) injection), model group (with tumor burden, received NS 100 µl×d(-1) injection) and treatment group (with tumor burden, received rh-endostatin 400 µg×d(-1) injection) for 28 days. The tumor volume and body weight of the mice were measured before and after administration. The expression of CD34, MMP-2, MMP-9, HIF-1α and VEGF in the myocardium and tumor were detected by immunohistochemistry. The vascular structure was observed by immunoenzymatic CD34 and Masson double staining.

RESULTSThe increase of tumor volume of the treatment group [(48.18 ± 37.31) mm(3)] was significantly lower than that in the model group [(113.80 ± 73.27) mm(3)). The changes of body weight was not significant different among the four groups. After treated with rh-endostatin, the expressions of MMP-9 and VEGF in tumors were significantly down-regulated, but the expressions of MMP-2 and HIF-1α in the tumor were not. The microvessel density (MVD) in the tumors of treatment group was significantly decreased compared with that of model group. The proportion of tumor vessels covered by collagen in the treatment group was increased compared with that of the model group. However, MVD and micrangium in myocardium were not changed significantly.

CONCLUSIONRh-endostatin can decrease the expression of MMP-9, VEGF and MVD, inhibit the tumor growth and normalize tumor micrangium in tumor but not weaken the MMPs and MVD of mature micrangium in myocadium.