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三七对人结肠癌细胞转移的影响。

Effects of Panax notoginseng on the Metastasis of Human Colorectal Cancer Cells.

作者信息

Hsieh Shu-Ling, Hsieh Shuchen, Kuo Yu-Hao, Wang Jyh-Jye, Wang Jinn-Chyi, Wu Chih-Chung

机构信息

* Department of Seafood Science, National Kaohsiung Marine University, Kaohsiung 81157, Taiwan.

† Department of Chemistry, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.

出版信息

Am J Chin Med. 2016;44(4):851-70. doi: 10.1142/S0192415X16500476. Epub 2016 May 24.

Abstract

The goal of this study was to investigate the effect of the Panax notoginseng ethanol extract (PNEE) on the regulation of human colorectal cancer (CRC) metastasis. The migratory, invasive, and adhesive abilities and the expression of metastasis-associated regulatory molecules in cultured human CRC cells (HCT-116) treated with the PNEE were analyzed in this study. The migratory and invasive abilities of HCT-116 cells were reduced after PNEE treatment. The incubation of HCT-116 cells with the PNEE for 24 h decreased MMP-9 expression and increased E-cadherin expression compared with the control group. The adhesion reaction assay indicated that treatment with the PNEE led to significantly decreased HCT-116 adhesion to endothelial cells (EA.hy926 cells). The integrin-1 protein levels in HCT-116 cells were significantly decreased following treatment with the PNEE. Similarly, the protein levels of E-selectin and intercellular adhesion molecule-1 (ICAM-1) were significantly decreased by treatment of the EA.hy926 endothelial cells with PNEE. A scanning electron microscope (SEM) examination indicated that HCT-116 cells treated with LPS combined with the PNEE had a less flattened and retracted shape compared with LPS-treated cells, and this change in shape was found to be a phenomenon of extravasation invasion. The transepithelial electrical resistance (TEER) of the EA.hy926 endothelial cell monolayer increased after incubation with the PNEE for 24 h. A cell-cell permeability assay indicated that HCT-116 cells treated with the PNEE displayed significantly reduced levels of phosphorylated VE-cadherin (p-VE-cadherin). These results demonstrate the antimetastatic properties of the PNEE and show that the PNEE affects cells by inhibiting cell migration, invasion, and adhesion and regulating the expression of metastasis-associated signaling molecules.

摘要

本研究的目的是探讨三七乙醇提取物(PNEE)对人结直肠癌(CRC)转移调控的影响。本研究分析了用PNEE处理的培养人CRC细胞(HCT-116)的迁移、侵袭和黏附能力以及转移相关调节分子的表达。PNEE处理后,HCT-116细胞的迁移和侵袭能力降低。与对照组相比,将HCT-116细胞与PNEE孵育24小时可降低MMP-9表达并增加E-钙黏蛋白表达。黏附反应试验表明,PNEE处理导致HCT-116对内皮细胞(EA.hy926细胞)的黏附显著降低。PNEE处理后,HCT-116细胞中的整合素-1蛋白水平显著降低。同样,用PNEE处理EA.hy926内皮细胞可显著降低E-选择素和细胞间黏附分子-1(ICAM-1)的蛋白水平。扫描电子显微镜(SEM)检查表明,与LPS处理的细胞相比,用LPS联合PNEE处理的HCT-116细胞形状更不扁平且更收缩,并且发现这种形状变化是一种外渗侵袭现象。将EA.hy926内皮细胞单层与PNEE孵育24小时后,其跨上皮电阻(TEER)增加。细胞间通透性试验表明,用PNEE处理的HCT-116细胞中磷酸化VE-钙黏蛋白(p-VE-钙黏蛋白)水平显著降低。这些结果证明了PNEE的抗转移特性,并表明PNEE通过抑制细胞迁移、侵袭和黏附以及调节转移相关信号分子的表达来影响细胞。

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