Kim Hyuck, Roh Hyo Sun, Kim Jai Eun, Park Sun Dong, Park Won Hwan, Moon Jin-Young
Department of Diagnostics, College of Korean Medicine, Dongguk University, Goyang 10326, Korea.
Department of Acupoint, College of Korean Medicine, Dongguk University, Dongguk-Ro 32, Goyang 10326, Korea.
Nutr Res Pract. 2016 Jun;10(3):259-64. doi: 10.4162/nrp.2016.10.3.259. Epub 2016 Mar 2.
BACKGROUND/OBJECTIVES: Stromal cell-derived growth factor 1 (SDF-1), also known as chemokine ligand 12, and chemokine receptor type 4 are involved in cancer cell migration. Compound K (CK), a metabolite of protopanaxadiol-type ginsenoside by gut microbiota, is reported to have therapeutic potential in cancer therapy. However, the inhibitory effect of CK on SDF-1 pathway-induced migration of glioma has not yet been established.
MATERIALS/METHODS: Cytotoxicity of CK in C6 glioma cells was determined using an EZ-Cytox cell viability assay kit. Cell migration was tested using the wound healing and Boyden chamber assay. Phosphorylation levels of protein kinase C (PKC)α and extracellular signal-regulated kinase (ERK) were measured by western blot assay, and matrix metallopeptidases (MMP) were measured by gelatin-zymography analysis.
CK significantly reduced the phosphorylation of PKCα and ERK1/2, expression of MMP9 and MMP2, and inhibited the migration of C6 glioma cells under SDF-1-stimulated conditions.
CK is a cell migration inhibitor that inhibits C6 glioma cell migration by regulating its downstream signaling molecules including PKCα, ERK1/2, and MMPs.
背景/目的:基质细胞衍生因子1(SDF-1),也称为趋化因子配体12,与趋化因子受体4型均参与癌细胞迁移。化合物K(CK)是原人参二醇型人参皂苷经肠道微生物群代谢产生的一种代谢产物,据报道在癌症治疗中具有治疗潜力。然而,CK对SDF-1途径诱导的胶质瘤迁移的抑制作用尚未得到证实。
材料/方法:使用EZ-Cytox细胞活力检测试剂盒测定CK对C6胶质瘤细胞的细胞毒性。采用伤口愈合实验和Boyden小室实验检测细胞迁移情况。通过蛋白质印迹法检测蛋白激酶C(PKC)α和细胞外信号调节激酶(ERK)的磷酸化水平,通过明胶酶谱分析检测基质金属肽酶(MMP)。
在SDF-1刺激条件下,CK显著降低了PKCα和ERK1/2的磷酸化水平、MMP9和MMP2的表达,并抑制了C6胶质瘤细胞的迁移。
CK是一种细胞迁移抑制剂,通过调节其下游信号分子(包括PKCα、ERK1/2和MMPs)来抑制C6胶质瘤细胞的迁移。