目的:研究六味地黄汤对DMBA诱发性乳腺癌抑制作用,及对肿瘤组织中血管内皮生长因子(VEGF)、基质金属蛋白酶-9(MMP-9)表达的影响。方法:将60只雌性SD大鼠随机分为空白对照组、DMBA模型组、六味地黄汤6.4、3.2、1.6 g/kg剂量组和阳性药物三苯氧胺组。除空白对照组外,每只大鼠灌胃两次DMBA(间隔1周,每次剂量0.1g/kg)诱发乳腺癌。同时开始给予药物干预,并触诊所有大鼠乳腺肿瘤发生情况并记录体重变化;诱导15周后处死动物,统计各组大鼠乳腺肿瘤的发病率,测量肿瘤重量,并采用ELISA法检测血清中环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP)含量,SP法免疫组化检测各组动物乳腺癌组织中VEGF、MMP-9的表达情况。结果:与模型组比较,六味地黄汤6.4g/kg剂量组大鼠乳腺肿瘤平均潜伏期显著延长,平均肿瘤体积、平均瘤重显著降低(P〈0.05);六味地黄汤6.4g/kg剂量组血清中cAMP含量及cAMP/cGMP显著降低;六味地黄汤1.6和6.4g/kg剂量组VEGF和MMP-9强阳性率均明显降低,且VEGF与MMP-9的表达呈正相关。结论:滋阴方药六味地黄汤可以抑制乳腺癌发生及恶化,可能的机制是通过干预乳腺癌组织中VEGF和MMP-9的表达。
Objective: To explore the effect of Liuwei Dihuang Decoction on expressions of vascular endothelial growth factor( VEGF) and matrix metalloproteinase-9( MMP-9) in brest cancer induced by 7,12-dimethylbenz( a) anthrancene( DMBA) in rats. Methods: The 60 female SD rats were randomly divided into 6 groups: the blank control group,the DMBA model group,6. 4,3. 2,1. 6 g /kg Liuwei Dihuang Decoction and tamoxifen( TAM) group. All rats were induced by DMBA( 0. 1g /kg,twice,one week interval),except for the blank control group,and were palpated weekly to monitor the tumor development,body weight were also recorded weekly. At the end of trial,the incidence of breast tumors in each group was computed. The level of serum cAMP,cGMP were detected by ELISA method. And the expressions of VEGF and MMP-9 in breast cancer tissues were detected using immunohistochemical SP method. Results: Comparing with the DMBA model group,the breast cancer incidence,number and volume of tumor in the 6. 4g /kg Liuwei Dihuang Decoction group and TAM group decreased significantly( P <0.05). The concentration of cAMP and cAMP/cGMP in serum was obviously lower in the groups treating with 6.4g/kg of Liuwei Dihuang Decoction. The strong-positive rate of VEGF and MMP-9 was significantly higher in the group treating with 1. 6,6. 4g /kg of Liuwei Dihuang Decoction than DMBA model group( P < 0. 05),and VEGF expression was positively correlated with MMP-9 expression in breast cancer. Conclusion: Liuwei Dihuang Decoction might inhibit the development and deterioration of breast cancer possibly through adjust the expressions of VEGF and MMP-9.