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首页> 外文期刊>Journal of Agricultural and Food Chemistry >Evaluation of Anti-invasion Effect of Resveratrol and Related Methoxy Analogues on Human Hepatocarcinoma Cells
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Evaluation of Anti-invasion Effect of Resveratrol and Related Methoxy Analogues on Human Hepatocarcinoma Cells

机译:白藜芦醇及相关甲氧基类似物对人肝癌细胞的抗侵袭作用评价

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Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is also highly metastatic. Metastasis is considered to be the major cause of death in cancer patients. Resveratrol (3,5,4'-trihydroxystilbene) and related analogues have been reported as candidates to prevent cancer growth and invasion. The bioactivity of resveratrol-related analogues could be altered due to the presence and positioning of methoxy groups on the basic resveratrol chemical structure. This study investigated the effects and mechanism of action of resveratrol and its methoxy analogues on invasion of human hepatocarcinoma cells. The migratory and invasive abilities of phorbol 12-myristate 13-acetate (PMA)-treated HepG2 and PMA-untreated Hep3B cells were both reduced in a dose-dependent manner by treatment with resveratrol and 3,5,4'-trimethoxy-trans-stilbene (MR-3). Upon incubation of PMα-Treated HepG2 cells with resveratrol (0-50 μM) or MR-3 (0-50 μM), the MMP-9 activity decreased but TIMP-1 protein increased in a dose-dependent manner. With resveratrol (0-50 μM) or MR-3 (0-1 μM) treatment on PMA-untreated Hep3B cells, both of the MMP-9 and MMP-2 activities decreased but TIMP-2 protein increased in a dose-dependent manner. These results suggest that resveratrol and its related methoxy analogue MR-3 might exert anti-invasive activity against hepatoma cells through regulation of MMP-2, MMP-9, TIMP-1, and TIMP-2. Further analysis with semiquantitative RT-PCR showed that the regulation of MMP-9 and TIMP-2 expressions by resveratrol and MR-3 in hepatoma cells may be on the transcriptional level but on the translational or post-translational level for TIMP-1.
机译:肝细胞癌(HCC)是最常见的肝癌类型,并且也是高度转移性的。转移被认为是癌症患者死亡的主要原因。据报道,白藜芦醇(3,5,4'-三羟基sti)和相关类似物可以预防癌症的生长和侵袭。白藜芦醇相关类似物的生物活性可能会由于白藜芦醇基本化学结构上甲氧基的存在和位置而改变。这项研究调查了白藜芦醇及其甲氧基类似物对人肝癌细胞侵袭的作用及其作用机理。经白藜芦醇和3,5,4'-三甲氧基-反-二苯乙烯(MR-3)。将PMα处理的HepG2细胞与白藜芦醇(0-50μM)或MR-3(0-50μM)孵育后,MMP-9活性降低,但TIMP-1蛋白以剂量依赖性方式增加。在未经PMA处理的Hep3B细胞上使用白藜芦醇(0-50μM)或MR-3(0-1μM)处理后,MMP-9和MMP-2活性均降低,但TIMP-2蛋白以剂量依赖性方式增加。这些结果表明,白藜芦醇及其相关的甲氧基类似物MR-3可能通过调节MMP-2,MMP-9,TIMP-1和TIMP-2发挥抗肝癌细胞的侵袭活性。用半定量RT-PCR进行的进一步分析表明,白藜芦醇和MR-3对肝癌细胞中MMP-9和TIMP-2表达的调节可能在TIMP-1的转录水平或翻译或翻译后水平。

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