Department of Medical Laboratory Science and Biotechnology, School of Pharmacy, China Medical University, Taichung 404, Taiwan, ROC.
Oncol Rep. 2011 Jul;26(1):177-84. doi: 10.3892/or.2011.1264. Epub 2011 Apr 15.
Epidemiological studies have demonstrated that a natural diet or consumption of fruits or vegetables can decrease the risk of cancer development. Cancer cells can migrate to and invade other organs or tissues that cause more difficulty to treat them and this also results in the need for treatments targeting multiple cellular pathways. Gallic acid (GA) has been demonstrated to possess multiple biological activities including anticancer function. However, no report exist on GA inhibited invasion and migration of human prostate cancer cells. We investigated the effects of migration and invasion in GA-treated PC-3 human prostate cancer cells with a series of in vitro experiments. Boyden chamber transwell assay was used to examine the migration and invasion of PC-3 cells. Western blotting, real-time PCR and gelatin zymography were used for determining the protein levels, gene expression and enzyme activities of matrix metalloproteinase-2 (MMP-2) and -9 in vitro. Results indicated that GA inhibited the invasion and migration of PC-3 cells and these effects are dose-dependent. GA inhibited the protein levels of MMP-2 and -9, son of sevenless homolog 1 (SOS1), growth factor receptor-bound protein 2 (GRB2), protein kinase C (PKC) and nuclear factor-κ B (NF-κB) p65, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), p38, p-AKT (Thr308) and p-AKT (Ser473), but it promoted the levels of phosphatidylinositol 3-kinase (PI3K) and AKT in PC-3 cells. GA also reduced the enzyme activities of MMP-2 and -9 in the examined cells. Moreover, the down-regulation of focal adhesion kinase (FAK) and Ras homolog gene family, member A (Rho A) mRNA expression levels, and up-regulation of the tissue inhibitor of metalloproteinase-1 (TIMP1) gene levels occurred in GA-treated PC-3 cells after 24 h treatment. Based on these observations, we suggest that GA might modulate through blocking the p38, JNK, PKC and PI3K/AKT signaling pathways and reducing the NF-κB protein level, resulting in the inhibition of MMP-2 and -9 of PC-3 human prostate cancer cells.
流行病学研究表明，天然饮食或水果、蔬菜的摄入可以降低癌症发展的风险。癌细胞可以迁移并侵袭其他器官或组织，这使得治疗更加困难，也需要针对多个细胞途径进行治疗。没食子酸（GA）已被证明具有多种生物学活性，包括抗癌功能。然而，目前尚无 GA 抑制人前列腺癌细胞侵袭和迁移的报道。我们通过一系列体外实验研究了 GA 处理的 PC-3 人前列腺癌细胞的迁移和侵袭。Boyden 室 Transwell 分析用于检测 PC-3 细胞的迁移和侵袭。Western blot、实时 PCR 和明胶酶谱分析用于测定体外基质金属蛋白酶-2（MMP-2）和 -9 的蛋白水平、基因表达和酶活性。结果表明，GA 抑制了 PC-3 细胞的侵袭和迁移，且呈剂量依赖性。GA 抑制了 MMP-2 和 -9、SOS1、生长因子受体结合蛋白 2（GRB2）、蛋白激酶 C（PKC）和核因子-κB（NF-κB）p65、c-Jun N-末端激酶（JNK）、细胞外信号调节激酶 1/2（ERK1/2）、p38、p-AKT（Thr308）和 p-AKT（Ser473）的蛋白水平，但促进了 PC-3 细胞中磷脂酰肌醇 3-激酶（PI3K）和 AKT 的水平。GA 还降低了所检查细胞中 MMP-2 和 -9 的酶活性。此外，GA 处理 24 小时后，PC-3 细胞中的黏着斑激酶（FAK）和 Ras 同源基因家族成员 A（Rho A）mRNA 表达水平下调，组织金属蛋白酶抑制剂 1（TIMP1）基因水平上调。基于这些观察结果，我们认为 GA 可能通过阻断 p38、JNK、PKC 和 PI3K/AKT 信号通路以及降低 NF-κB 蛋白水平来调节，从而抑制 PC-3 人前列腺癌细胞的 MMP-2 和 -9。
