Zhang Yi, Zhang Gan-Lin, Sun Xu, Cao Ke-Xin, Shang Ya-Wen, Gong Mu-Xin, Ma Cong, Nan Nan, Li Jin-Ping, Yu Ming-Wei, Yang Guo-Wang, Wang Xiao-Min
Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China.
School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China.
Molecules. 2017 May 15;22(5):787. doi: 10.3390/molecules22050787.
II (GYII), a Traditional Chinese Medicine (TCM) formula used in our hospital, has shown beneficial effects in cancer patients. In this study, we investigated the molecular mechanisms underlying the beneficial effects of GYII on murine breast cancer models. GYII showed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model. Additionally, GYII suppressed the proliferation of 4T1 and MCF-7 cells in a dose-dependent manner. A better inhibitory effect on 4T1 cell proliferation and migration was found in the decomposed recipes (DR) of GYII. Moreover, heparanase expression and the degree of angiogenesis were reduced in tumor tissues. Western blot analysis showed decreased expression of heparanase and growth factors in the cells treated with GYII and its decomposed recipes (DR2 and DR3), and thereby a reduction in the phosphorylation of extracellular signal-regulated kinase (ERK) and serine-threonine kinase (AKT). These results suggest that GYII exerts anti-tumor growth and anti-metastatic effects in the murine breast cancer model. The anti-tumor activity of GYII and its decomposed recipes is, at least partly, associated with decreased heparanase and growth factor expression, which subsequently suppressed the activation of the ERK and AKT pathways.
我院使用的中药配方II（GYII）已在癌症患者中显示出有益效果。在本研究中，我们调查了GYII对小鼠乳腺癌模型产生有益效果的分子机制。GYII在小鼠乳腺癌模型中对肿瘤生长和转移显示出显著的抑制作用。此外，GYII以剂量依赖的方式抑制4T1和MCF-7细胞的增殖。在GYII的拆方（DR）中发现对4T1细胞增殖和迁移有更好的抑制作用。此外，肿瘤组织中乙酰肝素酶的表达和血管生成程度降低。蛋白质印迹分析显示，用GYII及其拆方（DR2和DR3）处理的细胞中乙酰肝素酶和生长因子的表达降低，从而细胞外信号调节激酶（ERK）和丝氨酸-苏氨酸激酶（AKT）的磷酸化减少。这些结果表明，GYII在小鼠乳腺癌模型中发挥抗肿瘤生长和抗转移作用。GYII及其拆方的抗肿瘤活性至少部分与乙酰肝素酶和生长因子表达降低有关，这随后抑制了ERK和AKT途径的激活。
