Park Jung Sun, Kim Ki Min, Kim Mi Ha, Chang Hee Jung, Baek Min Kyung, Kim Seok Mo, Jung Young Do
The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Chonnam National University Medical School, Kwangju, Korea.
Anticancer Res. 2009 Jan;29(1):355-62.
Resveratrol, a grape polyphenol, is thought to have anti-inflammatory, cardioprotective, and cancer preventive properties. However, the mechanisms by which resveratrol might produce these effects are not clearly defined. A study was performed on whether resveratrol could prevent tumor cells from adhering to endothelial cells, which is an essential step during tumor metastasis. Phorbol 12-myristate 13-acetate (PMA) induced human fibrosarcoma HT1080 cells to adhere to endothelial ECV304 cells. Resveratrol inhibited PMA-induced HT1080 cells adhesion in a dose-dependent manner. To further study the mechanisms of this resveratrol-mediated blockade of tumor cell adhesion, the expression of the cell adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin were examined. PMA induced ICAM-1 expression in HT1080 cells. In contrast, the expression of VCAM-1 and E-selectin were not altered by PMA treatment. The increase in tumor cell adhesion to endothelial cells following PMA treatment was partially inhibited by ICAM-1 siRNA or neutralizing antibodies. Resveratrol reduced the PMA-induced ICAM-1 expression in HT1080 cells as determined by RT-PCR, flow cytometry and ELISA. As the induction of ICAM-1 requires activation of the transcription factor NF-kappaB, the effects of resveratrol on the activation of this factor in HT1080 cells was also investigated. Resveratrol inhibited the PMA-induced NF-kappaB activation and NF-kappaB-dependent luciferase activity. These results suggest that resveratrol may exert an antimetastatic effect by inhibiting NF-kappaB activation and ICAM-1 expression, leading to suppression of tumor cell adhesion to endothelial cells.
白藜芦醇是一种葡萄多酚，被认为具有抗炎、心脏保护和防癌特性。然而，白藜芦醇产生这些作用的机制尚不清楚。进行了一项关于白藜芦醇是否能阻止肿瘤细胞黏附于内皮细胞的研究，这是肿瘤转移过程中的一个关键步骤。佛波酯12 -肉豆蔻酸酯13 -乙酸酯（PMA）诱导人纤维肉瘤HT1080细胞黏附于内皮ECV304细胞。白藜芦醇以剂量依赖性方式抑制PMA诱导的HT1080细胞黏附。为进一步研究白藜芦醇介导的肿瘤细胞黏附阻断机制，检测了细胞黏附分子细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）和E-选择素的表达。PMA诱导HT1080细胞中ICAM-1表达。相反，PMA处理未改变VCAM-1和E-选择素的表达。PMA处理后肿瘤细胞与内皮细胞黏附的增加被ICAM-1 siRNA或中和抗体部分抑制。通过逆转录-聚合酶链反应（RT-PCR）、流式细胞术和酶联免疫吸附测定（ELISA）确定，白藜芦醇降低了PMA诱导的HT1080细胞中ICAM-1的表达。由于ICAM-1的诱导需要转录因子核因子κB（NF-κB）的激活，还研究了白藜芦醇对HT1080细胞中该因子激活的影响。白藜芦醇抑制PMA诱导的NF-κB激活和NF-κB依赖性荧光素酶活性。这些结果表明，白藜芦醇可能通过抑制NF-κB激活和ICAM-1表达发挥抗转移作用，从而抑制肿瘤细胞与内皮细胞的黏附。
