咖啡酸苯乙酯通过 C6 神经胶质瘤细胞 p75（NTR）发挥抗肿瘤进展潜能。

Antitumor progression potential of caffeic acid phenethyl ester involving p75(NTR) in C6 glioma cells.

机构信息

Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan.

出版信息

Chem Biol Interact. 2010 Dec 5;188(3):607-15. doi: 10.1016/j.cbi.2010.09.002. Epub 2010 Sep 15.

DOI:10.1016/j.cbi.2010.09.002

PMID:20836997

Abstract

The previous data showed that caffeic acid phenethyl ester (CAPE), a component of propolis, possesses inducing cell cycle arrest and antiproliferation effect on C6 glioma cells in vitro and in vivo. In the present study, C6 glioma cells treated with CAPE resulted in morphological changes to an astrocytic phenotype and increased the expression of glial differentiation marker proteins including glial fibrillary acidic protein (GFAP) and S-100β. In addition, with scratch assay and Boyden chamber assay, CAPE exhibited inhibitory effects on the motility and invasion of C6 glioma cells. Furthermore, CAPE induced the expression of nerve growth factor (NGF) and p75 neurotrophin receptor (p75(NTR)), which were involved in neural cell differentiation. CAPE could also inhibit the activity of matrix metalloproteinases (MMPs) and induce the expression of RhoB, a tumor suppressor. To examine the involvement of p75(NTR) in the anti-invasive property of CAPE, Western blotting and Boyden Chamber assay were performed by addition of an anti-p75(NTR) antibody in C6 cells. The results showed that blocking p75(NTR) could decrease the CAPE-induced expression of RhoB and the inactivation of MMP-2, -9 as well as the anti-invasion effect in C6 glioma cells. Furthermore, CAPE suppressed IκB-α phosphorylation which was down stream of p75(NTR). Finally, the effect of CAPE on metastasis by lung colonization of the tumor cell in nude mice was also evaluated. It was found that the groups of nude mice injected with CAPE-pretreated cells could decrease both lung size and weight as compared to the positive control group which did not receive CAPE treatment. In addition, histological examination of the mouse lung sections showed that the CAPE-treated group inhibited the metastasis of C6 glioma cells. These data suggest CAPE possesses antitumor progression potential.

摘要

先前的数据表明，咖啡酸苯乙酯（CAPE）是蜂胶的一种成分，具有体外和体内诱导 C6 神经胶质瘤细胞周期停滞和抗增殖作用。在本研究中，CAPE 处理的 C6 神经胶质瘤细胞发生形态变化，表现为星形胶质细胞表型，并增加神经胶质分化标志物蛋白的表达，包括神经胶质纤维酸性蛋白（GFAP）和 S-100β。此外，划痕试验和 Boyden 室试验表明，CAPE 对 C6 神经胶质瘤细胞的迁移和侵袭具有抑制作用。此外，CAPE 诱导神经生长因子（NGF）和 p75 神经营养素受体（p75（NTR））的表达，这两种物质参与神经细胞分化。CAPE 还可以抑制基质金属蛋白酶（MMPs）的活性，并诱导肿瘤抑制因子 RhoB 的表达。为了研究 p75（NTR）在 CAPE 抗侵袭特性中的作用，通过在 C6 细胞中添加抗 p75（NTR）抗体进行 Western 印迹和 Boyden 室试验。结果表明，阻断 p75（NTR）可以降低 CAPE 诱导的 RhoB 表达以及 MMP-2、-9 的失活和 C6 神经胶质瘤细胞的抗侵袭作用。此外，CAPE 抑制了 p75（NTR）下游的 IκB-α 磷酸化。最后，还评估了 CAPE 对裸鼠肿瘤细胞肺定植转移的影响。结果发现，与未接受 CAPE 治疗的阳性对照组相比，注射 CAPE 预处理细胞的裸鼠组的肺部大小和重量均降低。此外，对小鼠肺切片的组织学检查表明，CAPE 处理组抑制了 C6 神经胶质瘤细胞的转移。这些数据表明 CAPE 具有抗肿瘤进展的潜力。