重组人血管内皮抑素与多西紫杉醇不同顺序用药调控移植瘤组织MMP及抗瘤效应观察

BACKGROUND AND OBJECTIVE: The aim of this study is to observe the changes of MMP-2 and its regulators, and to investigate the mechanism of the two administration sequences of recombinant human endostatin (rh-endostatin) and docetaxel. METHODS: The experiment was performed as 2 stages. Firstly, nude mice with xenograft tumor were randomized into 2 groups as rh-endostatin-treated group with rh-endostatin 400 μg·d(-1), d1-d14 and docetaxel-traeted group with docetaxel 10 mg·kg(-1)·3d(-1), d1-d14. Secondly, nude mice with xenograft tumor were randomized into 3 groups as concurrent administration group (rh-endostatin 400 μg·d(-1), d1-d35, docetaxel 10 mg·kg(-1)·3d(-1), d1-d19), endo-first group (rh-endostatin 400 μg·d(-1), d1-d35, docetaxel 10 mg·kg(-1)·3d(-1), d16-d34) and model group (positive control, mice burdened tumor without treatment). The volume of tumor was measured during treatment. Detection of the expressions of MMP-2, TIMP-2, EMMPRIN and the count of microvessel density (MVD) by immunohistochemistry stain examination were carried out at the end of experiment. RESULTS: Compared with the docetaxel-treated group, more obvious down-regulation of expression of MMP-2, EMMPRIN (P=0.024, P=0.081) were observed in rh-endostatin-treated group. No significant difference was found in TIMP-2 expression between the 2 groups. In combined treatment groups, at the endpoint tumor volumes of concurrent administration group and the endo-first group were remarkably smaller than that in model group (P < 0.001, P=0.003). According to the administration procedure, concurrent administration inhibited tumor growth ber than endo-first treatment did. Both of the combined groups down-regulated the expression of MMP-2 and decreased microvessel density (P < 0.05). Compared with model group, the expression of TIMP-2 was upregulated (P=0.001) as well as EMMPRIN down-regulated (P=0.018) in concurrent administration group. Oppositely, the same results were not observed in the endo-first group. CONCLUSION: The schedule of the concurrent administration group could inhibit the tumor growth better, and it down-regulated MMP-2 expression through TIMP-2 and EMMPRIN, and thus slow down the tumor growth superiorly to another schedule of treatment.