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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 study the inhibitory effect of Liuwei Dihuang decoction on DMBA-induced breast cancer and its effect on the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in tumor tissue. Methods: Sixty female SD rats were randomly divided into blank control group, DMBA model group, Liuwei Dihuang Decoction 6.4,3.2,1.6 g / kg dose group and the positive drug tamoxifen group. In addition to the blank control group, each rat was intragastric DMBA (interval of 1 week, each dose of 0.1g / kg) induced breast cancer. At the same time began to give the drug intervention and palpation of all breast cancer incidence and record body weight changes; 15 weeks after induction of animals were sacrificed, the incidence of breast cancer in each group statistics, tumor weight measurement, and ELISA assay serum The levels of cAMP and cGMP were detected by immunohistochemistry. The expressions of VEGF and MMP-9 in breast cancer tissues were detected by SP immunohistochemistry. Results: Compared with the model group, the average latency of mammary gland in Liuwei Dihuang Decoction 6.4g / kg dose group was significantly prolonged (P <0.05), and the average tumor volume and average tumor weight were significantly decreased (P <0.05) The content of cAMP and cAMP / cGMP were significantly decreased. The strong positive rates of VEGF and MMP-9 in the 1.6 and 6.4 g / kg doses of Liuweidihuang Decoction were significantly decreased, and the expressions of VEGF and MMP-9 were positively correlated. Conclusion: Ziyin Recipe Liuweidihuang Decoction can inhibit the occurrence and progression of breast cancer. The possible mechanism is through the intervention of VEGF and MMP-9 expression in breast cancer tissues.