Therapeutic Effects of Matrine on Primary and Metastatic Breast Cancer
Therapeutic Effects of Matrine on Primary and Metastatic Breast Cancer
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苦参碱对原发性和转移性乳腺癌的治疗作用
DOI：
10.1142/s0192415x10008512
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发表时间：
2010-01-01
影响因子：
5.7
通讯作者：
Sun, Xueying
中科院分区：
文献类型：
--
作者：
Li, Hali;Tan, Gang;Sun, Xueying
苦参碱是从传统中药苦参中提取的主要成分之一，对几种类型的癌细胞显示出抗癌活性。本研究旨在评估苦参碱对原发性和转移性乳腺癌的治疗效果。MTT、流式细胞术和激光扫描共聚焦显微镜实验结果显示，苦参碱对人MCF-7和小鼠4T1乳腺癌细胞的体外活性有一定的抑制作用，并呈剂量依赖性。在同源Balb/c小鼠高转移性4T1乳腺癌模型中，苦参碱以剂量依赖的方式抑制原发肿瘤的生长及其向肺和肝脏的转移。与对照组相比，经抗ki -67抗体免疫染色的小鼠肿瘤具有较小的增殖指数，tunel染色的小鼠肿瘤具有较大的凋亡指数，抗cd31a抗体免疫染色的小鼠肿瘤具有较小的微血管密度。Western blot分析肿瘤均质液显示，苦参碱治疗降低Bcl-2/Bax比值，下调VEGF和VEGFR-2表达，增加caspase-3和caspase-9的激活。这项研究表明，苦参碱可能是一种有效的药物，从一种天然资源，治疗转移性乳腺癌，因为它具有抗凋亡，抗增殖和抗血管生成的活性。
Matrine, one of the main components extracted from a traditional Chinese herb, Sophora flavescens Ait, has displayed anti-cancer activity in several types of cancer cells. This study aims to evaluate the therapeutic benefits of matrine on primary and metastatic breast cancer. Matrine inhibited the viability of and induced apoptosis in human MCF-7 and mouse 4T1 breast cancer cells in a dose-dependent manner in vitro as shown by MTT assay, flow cytometry and laser scanning confocal microscopy. Administration of matrine inhibited the growth of primary tumors and their metastases to lungs and livers, in a dose-dependent manner, in a highly metastatic model of 4T1 breast cancer established in syngeneic Balb/c mice. Tumors from matrine-treated mice had a smaller proliferation index, shown by immunostaining with an anti-Ki-67 antibody, a greater apoptosis index, shown by TUNEL-staining, and a less microvessel density, shown by immunostaining with an anti-CD31 A antibody, compared to the controls. Western blot analysis of tumoral homogenates indicated that matrine therapy reduced the ratio of Bcl-2/Bax, downregulated the expressions of VEGF and VEGFR-2, and increased the activation of caspase-3 and caspase-9. This study suggests matrine may be a potent agent, from a natural resource, for treating metastatic breast cancer because of its anti-apoptotic, anti-proliferative and anti-angiogenic activities.