Fisetin inhibits liver cancer growth in a mouse model: Relation to dopamine receptor.
Fisetin inhibits liver cancer growth in a mouse model: Relation to dopamine receptor.
复制标题
DOI：
10.3892/or.2017.5676
复制
发表时间：
2017-07
期刊：
影响因子：
4.2
通讯作者：
Yao HL
中科院分区：
文献类型：
--
作者：
Liu XF;Long HJ;Miao XY;Liu GL;Yao HL
非瑟酮（3，3 ′，4 ′，7-四羟基黄酮）是一种天然丰富的黄酮类化合物，存在于多种蔬菜和水果中。据报道，非瑟酮具有多种积极的生物学作用，包括抗增殖、抗癌、抗氧化和神经保护作用。多巴胺受体（Dopamine receptor，DRs）属于G蛋白偶联受体家族，约50%的现代药物都以其为靶点。DR由多种蛋白质组成，作为细胞内信号转导细胞外刺激的功能。我们发现非瑟酮作为DR 2激动剂抑制肝癌细胞的增殖、迁移和侵袭。激活Caspase-3信号传导以诱导非瑟酮给药的细胞凋亡。此外，在非瑟酮处理的肝癌细胞中，TGF-β1也被抑制，从而减少上皮-间质转化（EMT）。此外，非瑟酮下调VEGFR 1，p-ERK 1/2，p38和pJNK，改善肝癌进展。体内实验表明，非瑟酮对小鼠原位移植瘤有明显的抑制作用，并伴有存活率的延长和多巴胺水平的升高。总之，这些结果表明了一种抑制与DR 2调节相关的肝癌进展的新治疗策略，表明多巴胺可能在肝癌进展中具有重要意义。
Fisetin (3,3′,4′,7-tetrahydroxyflavone), a natural abundant flavonoid, is produced in different vegetables and fruits. Fisetin has been reported to relate to various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. Dopamine receptors (DRs) belonging to G protein-coupled receptor family, are known as the target of ~50% of all modern medicinal drugs. DRs consist of various proteins, functioning as transduction of intracellular signals for extracellular stimuli. We found that fisetin performed as DR2 agonist to suppress liver cancer cells proliferation, migration and invasion. Caspase-3 signaling was activated to induce apoptosis for fisetin administration. Furthermore, TGF-β1 was also inhibited in fisetin-treated liver cancer cells, reducing epithelial-mesenchymal transition (EMT). Additionally, fisetin downregulated VEGFR1, p-ERK1/2, p38 and pJNK, ameliorating liver cancer progression. In vivo, the orthotopically implanted tumors from mice were inhibited by fisetin adminisatration accompanied by prolonged survival rate and higher levels of dopamine. Together, the results indicated a novel therapeutic strategy to suppress liver cancer progression associated with DR2 regulation, indicating that dopamine might be of importance in liver cancer progression.