Jayakumar Thanasekaran, Chiu Chong-Chi, Wang Shwu-Huey, Chou Duen-Suey, Huang Yung-Kai, Sheu Joen-Rong
School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
Department of Pharmacology and Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan.
J Cancer Res Ther. 2014 Jan-Mar;10(1):43-9. doi: 10.4103/0973-1482.131365.
Matrix metalloproteinases (MMPs) play important roles in the invasion and migration of cancer cells. In melanoma, several signaling pathways are constitutively activated. Among these, the mitogen-activated protein kinase (MAPKs) signaling pathways are activated through multiple signal transduction molecules and appear to play major roles in melanoma progression. Therefore, the inhibition of MAPK signaling might be a crucial role for the treatment of melanoma cancer.
We examined the anticancer effect of CME-1, a novel water-soluble polysaccharide fraction, isolated from Cordyceps sinensis mycelia on B16-F10 melanoma cells.
B16-F10 cells were exposed to different concentrations of CME-1 (250, 500 and 800 μg/ml) for 24 h in 5% CO² incubator at 37°C. Western blot analysis was performed to detect the expression of MMP-1, p-p38 MAPK, p-ERK1/2, and IkB-α in B16-F10 cells. Cell migration test was performed by wound healing migration assay.
CME-1 suppresses cell migration in a concentration-dependent manner. Western blotting analysis revealed that CME-1 led to the reduction on the expression levels of MMP-1 and down regulated the expression of phosphorylated extracellular signal-regulated kinase (ERK1/2 and p38 mitogen-activated protein kinase (p38 MAPK). CME-1 restored the IkB-degradation in B16F10 cells.
These results indicate that CME-1 inhibited MMP-1 expressions in B16F10 melanoma cells through either NF-kB or ERK/p38 MAPK down regulation thereby inhibiting B16F10 cell migration. Therefore, we proposed that CME-1 might be developed as a therapeutic potential candidate for the treatment of cancer metastasis.
基质金属蛋白酶(MMPs)在癌细胞的侵袭和迁移中起重要作用。在黑色素瘤中,多种信号通路持续激活。其中,丝裂原活化蛋白激酶(MAPKs)信号通路通过多种信号转导分子被激活,并且似乎在黑色素瘤进展中起主要作用。因此,抑制MAPK信号可能是治疗黑色素瘤的关键作用。
我们研究了从中华虫草菌丝体中分离出的一种新型水溶性多糖组分CME-1对B16-F10黑色素瘤细胞的抗癌作用。
将B16-F10细胞在37°C、5% CO²培养箱中暴露于不同浓度的CME-1(250、500和800μg/ml)24小时。进行蛋白质免疫印迹分析以检测B16-F10细胞中MMP-1、p-p38 MAPK、p-ERK1/2和IkB-α的表达。通过伤口愈合迁移试验进行细胞迁移测试。
CME-1以浓度依赖性方式抑制细胞迁移。蛋白质免疫印迹分析显示,CME-1导致MMP-1表达水平降低,并下调磷酸化细胞外信号调节激酶(ERK1/2)和p38丝裂原活化蛋白激酶(p38 MAPK)的表达。CME-1恢复了B16F10细胞中IkB的降解。
这些结果表明,CME-1通过下调NF-κB或ERK/p38 MAPK抑制B16F10黑色素瘤细胞中MMP-1的表达,从而抑制B16F10细胞迁移。因此,我们提出CME-1可能被开发为治疗癌症转移的潜在治疗候选物。