黑米花青素对HER-2/neu高表达人乳腺癌细胞株MDA-MB-453移植瘤血管生成的影响

Effect of black rice anthocyanins on angiogenesis in transplanted tumor of human breast cancer MDA-MB-453 cells over-expressing HER-2/neu

目的观察黑米花青素对HER-2/neu高表达人乳腺癌细胞株MDA-MB-453移植瘤血管生成的影响。方法以24只雌性BALB/c裸鼠建立MDA-MB-453细胞移植瘤模型,按照完全随机设计原则平均分入对照组、VEGF组、黑米花青素组和联合组4个处理组,分别以VEGF和黑米花青素提取物进行单独和联合干预;免疫组织化学法检测瘤组织核抗原Ki-67和Ⅷ因子相关抗原表达,评价移植瘤肿瘤细胞生长能力和瘤组织微血管密度(MVD)的变化;Western blot检测瘤组织促血管生成因子MMP-2、MMP-9和uPA表达水平的变化。结果相对于对照组,黑米花青素组瘤体积、MVD值和促血管生成因子的表达水平均显著降低(P<0.05),VEGF组上述指标则均有明显升高(P<0.05),联合组上述指标同对照组之间均无显著差异。相对于VEGF组,黑米花青素组和联合组的上述指标均有显著降低(P<0.05),其中黑米花青素组瘤体积有非常显著的降低(P<0.01)。与对照组相比,黑米花青素组核抗原Ki-67表达强阳性的细胞数显著减少,VEGF组核抗原Ki-67表达强阳性的细胞数显著增多。结论黑米花青素可能通过抑制移植瘤内血管生成而抑制肿瘤生长。

Objective To evaluate the effect of black rice anthocyanins on angiogenesis in transplanted tumor of human breast cancer MDA-MB-453 cells over-expressing HER-2/neu.Methods Twenty-four female BALB/c nude mice were used to establish transplanted tumor models with MDA-MB-453 cells.The mice were equally randomized into 4 groups including the control group,the VEGF group,the black rice anthocyanins group and the co-treatment group,with the intervention of VEGF and/or black rice anthocyanin-rich extract. Immunohistocheinistry was used to detect the expression of nuclear antigen Ki-67 and factor Ⅷ related antigen in order to evaluate alternations of tumor cells growth ability and tumor microvessel density （MVD） respectively. Western blotting was used to examine the expression of tumor angiogenesis-related factors MMP-2, MMP-9 and uPA. Results Compared to the control group, statistically significant decrease was observed in the black rice anthocyanins group on items of tumor volume, MVD value and the expression levels of tumor angiogenesis-related factors, with each P value lower than 0.05. Also, statistically significant increase was observed in the VEGF group on the items described above, with each P value lower than 0.05. There are no significant differences between the co-treatment group and the control group on these items described above. On the other hand, significant decrease of these items described above in black rice anthocyanins group as well as the co-treatment group were observed in comparison against the VEGF group, with each P values lower than 0.05. Besides, the amount of cells with strong positive Ki-67 staining were dramatically increased in the VEGF group and decreased in the black rice anthocyanins group compared to the control group. Conclusion Black rice anthocyanins might inhibit the growth of transplanted tumor of human breast cancer via tumor angiogenesis repression.