异种MMP-2 DNA疫苗联合小剂量顺铂治疗肿瘤转移的实验研究

Objective To evaluate the cooperating effect on whether the chicken homologous matrix metalloproteinase-2 (c-MMP-2) vaccine combined with low-dose cisplatin (DDP) can enhance the treatment efficacy of tumor metastasis. Methods The eukaryotic expression plasmid encoding chicken homologous MMP-2 was constructed by recombinant DNA technique. In this experiment, the lung metastasis model of murine colon adenocarcinoma (C26) was established in 6- to 8- weeks of age female BALB/c mice, and then treated with 0.9% NaCl solution (NS), DDP, c-MMP-2, or c-MMP-2 combined DDP. The number of tumor metastasis nodules on murine lung surface was counted and the lungs were weighed after the completion of above treatments. The tumor microvessel density (MVD) and cell apoptosis were evaluated by immunohistochemical and TUNEL methods. The titer and type of autoantibodies against MMP-2 in serum of mice were evaluated by enzyme-linked immunosorbent assay (ELISA). Results Compared with three other control groups, the combined treatment group significantly decreased the number of tumor metastasis nodules on lung surface and markedly the weight of murine lungs. The immunohistochemical analysis of tumor demonstrated a decreased MVD and a higher apoptosis cell rate happening to the combined treatment group. Autoantibodies against MMP-2 in serum of mice were, by ELISA, found in c-MMP-2 group and c-MMP-2 combined DDP group. Conclusion The antitumor effect of DDP can be potentiated by c-MMP-2. Thus the combination of c-MMP-2 and DDP results in an additive effect on the treatment of tumor metastasis.