摘要目的 观察肿瘤抑素改造后所得血管生成抑制相关肽(21肽)的抗血管生成活性及对裸鼠移植卵巢癌的抑制作用.方法 用亲和层析法纯化21肽.观察接种SKOV3细胞系的裸鼠经21肽治疗后的肿瘤生长情况,检测21肽对肿瘤组织的微血管密度和免疫组织化学指标的影响.结果 经21 d的治疗后,21肽组平均抑瘤率可达53.17%.21肽组肿瘤组织微血管密度(CD34表达)为6.324±1.643,与对照组(16.127±2.535)比较明显降低(P＜0.05).21肽组肿瘤组织的增殖细胞核抗原(PCNA)、血管内皮生长因子(VEGF)、基质金属蛋白酶2(MMP-2)呈低表达(P＜0.01),而基质金属蛋白酶抑制因子2(TIMP-2)呈高表达(P＜0.01).结论 21肽具有显著的抗血管生成活性,对卵巢癌具有较好的抑制作用,其抑制卵巢癌的作用机制可能与其降低新生血管形成和调解血管生成相关因子的表达有关.

abstractsObjective To evaluate the anti-angiogenic activity of peptide 21 obtained by modification of tumstatin,and its inhibitory effect on the growth and metastasis of human ovarian cancer transplanted in nude mice.Methods The peptide 21 was purified by affinity chromatography.Human ovarian cancer SKOV3 cells were inoculated in nude mice and the transplanted tumor was treated with the peptide 21 to observe the tumor growth and metastasis.The microvessel density (MVD) and immunohistochemical staining index of PCNA,VEGF and MMP-2 and TIMP-2 were performed to assess the inhibitory effect of the peptide 21.Resuits In the nude mice at 21 days after peptide 21 treatment,the inhibition rate of tumor growth was 53.17%,the tumor microvessel density was significantly reduced(P＜0.05),the expression of PCNA,VEGF and MMP-2 were significantly lower(P＜0.01),and TIMP-2 expression was significantly higher(P＜0.01)in comparison with that of control group.Conclusion The peptide 21 generated in this study has a significant anti-angiogenetic activity,showing significant inhibitory effect on the growth of human ovarian cancer transplanted in nude mice.The mechanism of its inhibitory action on ovarian cancer growth may be mediated by reduction of neovascularization and reduction of expression of angiogenetic factors.