Suppression of Human Breast Cancer Cell Metastasis by Coptisine in Vitro
Suppression of Human Breast Cancer Cell Metastasis by Coptisine in Vitro
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DOI：
10.7314/apjcp.2014.15.14.5747
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Xia, Xue-Lan
中科院分区：
文献类型：
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作者：
Li, Jing;Qiu, Dong-Min;Xia, Xue-Lan
背景资料：黄连碱是从黄连中提取的一种异喹啉类生物碱，具有抗糖尿病、抗菌、抗病毒等多种生物活性。然而，黄连碱是否具有抗肿瘤转移的作用尚不清楚。材料与方法：用台盼蓝法观察黄连碱对高转移性人乳腺癌细胞MDA-MB-231增殖的影响，用明胶粘附法、创伤愈合法和基质胶侵袭小室法观察黄连碱对细胞粘附、迁移和侵袭的影响。采用RT-PCR方法检测两种基质金属蛋白酶（MMP）的表达，即MMP-9、MMP-2及其特异性抑制剂TIMP-1、TIMP-2。结果如下：黄连碱明显抑制粘附到ECM涂层基板，伤口愈合迁移，并通过基质胶在MDA-MB-231乳腺癌细胞的侵袭。RT-PCR结果显示黄连碱在mRNA水平上降低了MDA-MB-231细胞ECM降解相关基因MMP-9的表达，上调了TIMP-1的表达，而对MMP-2及其特异性抑制剂TIMP-2的表达无影响。结论：结果表明，黄连碱能抑制MDA-MB-231乳腺癌细胞的粘附、迁移和侵袭，其抗转移作用可能与MMP-9表达下调和TIMP-1表达上调有关。黄连碱可能是一种潜在的乳腺癌治疗药物。
Background: Coptisine, an isoquinoline alkaloid extracted from Coptidis rhizoma, has many biological activities such as antidiabetic, antimicrobial and antiviral actions. However, whether coptisine exerts anti-cancer metastasis effects remains unknown. Materials and Methods: Effects of coptisine on highly metastatic human breast cancer cell MDA-MB-231 proliferation were evaluated by trypan blue assay and on cell adhesion, migration and invasion by gelatin adhesion, wound-healing and matrigel invasion chamber assays, respectively. Expression of two matrix metalloproteinases ( MMPs), MMP-9, MMP-2 and their specific inhibitors tissue inhibitor of metalloproteinase 1 (TIMP-1) and tissue inhibitor of metalloproteinase 2 (TIMP-2) were analyzed by RT-PCR. Results: Coptisine obviously inhibited adhesion to an ECM-coated substrate, wound healing migration, and invasion through the matrigel in MDA-MB-231 breast cancer cells. RT-PCR revealed that coptisine reduced the expression of the ECM degradation-associated gene MMP-9 at the mRNA level, and the expression of TIMP-1 was up-regulated in MDA-MB-231 cells, while the expression of MMP-2 and its specific inhibitor TIMP-2 was not affected. Conclusions: Taken together, our data showed that coptisine suppressed adhesion, migration and invasion of MDA-MB-231 breast cancer cells in vitro, the down-regulation of MMP-9 in combination with the increase of TIMP-1 possibly contributing to the anti-metastatic function. Coptisine might be a potential drug candidate for breast cancer therapy.