Wu Hongzhong, Liang Xin, Fang Yishi, Qin Xiaoran, Zhang Yuanxing, Liu Jianwen
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
Biomed Pharmacother. 2008 Nov;62(9):613-21. doi: 10.1016/j.biopha.2008.06.036. Epub 2008 Jul 9.
Resveratrol has been shown recently to exhibit antimetastatic effect on various human solid tumors. However, the possible molecular mechanism for its antimetastatic action needs to be elucidated. In this study, we investigated the effect of resveratrol on metastasis potential of colon carcinoma cells under normoxia and hypoxia in vitro. These results showed that, resveratrol can restrict the migration, adhesion, invasion and MMP-9 and MMP-2 secretion in Lovo cells cultured under normoxia and hypoxia. Hypoxia and iron chelator 2,2'-dipyridyl treatment can stimulate the invasion and migration enhancement of Lovo cells, while resveratrol exhibited substantial resistance on the metastasis potential stimulation by inhibiting the mRNA expression of VEGF and MMP-9 in colon carcinoma cells under normoxia and hypoxia, reducing HIF-1 alpha protein expression under hypoxia. Also, iron chelator 2,2'-dipyridyl treatment showed approximately the same effect on metastasis potential as Lovo cells cultured under hypoxia. These data demonstrated that, the antimetastatic effect of resveratrol under hypoxia were associated with the restriction of HIF-1 alpha protein expression and stabilization, which could be a promising drug target for resveratrol in the development of an effective chemopreventive and anticancer therapy in human tumors.
白藜芦醇最近已被证明对多种人类实体瘤具有抗转移作用。然而，其抗转移作用的可能分子机制仍有待阐明。在本研究中，我们在体外常氧和缺氧条件下研究了白藜芦醇对结肠癌细胞转移潜能的影响。这些结果表明，白藜芦醇可抑制常氧和缺氧培养的Lovo细胞的迁移、黏附、侵袭以及MMP-9和MMP-2的分泌。缺氧和铁螯合剂2,2'-联吡啶处理可刺激Lovo细胞侵袭和迁移增强，而白藜芦醇通过抑制常氧和缺氧条件下结肠癌细胞中VEGF和MMP-9的mRNA表达、降低缺氧条件下HIF-1α蛋白表达，对转移潜能刺激表现出显著抗性。此外，铁螯合剂2,2'-联吡啶处理对转移潜能的影响与缺氧培养的Lovo细胞大致相同。这些数据表明，白藜芦醇在缺氧条件下的抗转移作用与HIF-1α蛋白表达的限制和稳定有关，这可能是白藜芦醇在人类肿瘤有效化学预防和抗癌治疗开发中一个有前景的药物靶点。
