Lin Chien-Liang, Hsieh Shu-Ling, Leung Wan, Jeng Jiiang-Huei, Huang Guan-Cheng, Lee Chining-Ting, Wu Chih-Chung
Department of Pharmacy, Yuan's General Hospital, Kaohsiung 802, Taiwan, R.O.C.
Department of Seafood Science, National Kaohsiung Marine University, Kaohsiung 811, Taiwan, R.O.C.
Int J Oncol. 2016 Aug;49(2):629-38. doi: 10.3892/ijo.2016.3574. Epub 2016 Jun 9.
2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (THSG), a major component of Polygonum multiflorum Thunb (He-Shou-Wu), has been reported to exhibit antioxidant and anti-inflammatory effects. However, its anti-metastatic effect against colorectal cancer is still unclear. In this study, cell migration, invasion and adhesion abilities as well as metastasis-associated protein and NF-κB pathway signaling factor expression were analyzed after treating HT-29 cells with THSG. According to the results, the migration and invasiveness of HT-29 cells were reduced after treatment with 5 or 10 mM THSG (p<0.05). Additionally, the levels of matrix metalloproteinase-2 (MMP-2) and phosphorylated VE-cadherin in HT-29 cells were reduced and the transepithelial electrical resistance (TEER) of EA.hy926 endothelial cell monolayers was increased after incubation in THSG for 24 h (p<0.05). Cell adhesion ability and the E-selectin and intercellular adhesion molecule-1 (ICAM-1) protein levels were reduced when EA.hy926 endothelial cells were treated with THSG (p<0.05). In addition, the cytoplasmic phosphorylation of IκB, the nuclear p65 level and the DNA-binding activity of NF-κB were reduced after treating HT-29 or EA.hy926 cells with 5 or 10 mM THSG (p<0.05). These results suggest that THSG inhibits HT-29 cell metastasis by suppressing cell migration, invasion and adhesion. Furthermore, THSG inhibits metastasis-associated protein expression by suppressing NF-κB pathway activation.
2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷(THSG)是何首乌的主要成分,据报道具有抗氧化和抗炎作用。然而,其对结直肠癌的抗转移作用仍不清楚。在本研究中,用THSG处理HT-29细胞后,分析了细胞迁移、侵袭和黏附能力以及转移相关蛋白和NF-κB信号通路信号因子的表达。结果显示,用5或10 mM THSG处理后,HT-29细胞的迁移和侵袭能力降低(p<0.05)。此外,在THSG中孵育24小时后,HT-29细胞中基质金属蛋白酶-2(MMP-2)和磷酸化VE-钙黏蛋白的水平降低,EA.hy926内皮细胞单层的跨上皮电阻(TEER)增加(p<0.05)。用THSG处理EA.hy926内皮细胞时,细胞黏附能力以及E-选择素和细胞间黏附分子-1(ICAM-1)蛋白水平降低(p<0.05)。此外,用5或10 mM THSG处理HT-29或EA.hy926细胞后,IκB的细胞质磷酸化、核p65水平和NF-κB的DNA结合活性降低(p<0.05)。这些结果表明,THSG通过抑制细胞迁移、侵袭和黏附来抑制HT-29细胞转移。此外,THSG通过抑制NF-κB信号通路激活来抑制转移相关蛋白的表达。