Ou Xiuyuan, Chen Yan, Cheng Xinxin, Zhang Xumeng, He Qiyang
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China.
Academy of the State Administration of Grain, Beijing 100037, P.R. China.
Oncol Rep. 2014 Dec;32(6):2803-9. doi: 10.3892/or.2014.3512. Epub 2014 Sep 23.
Resveratrol, a natural polyphenolic phytochemical, has received considerable attention due to its potential chemopreventive and chemotherapeutic properties. In the present study, we first evaluated the growth-inhibitory effect of resveratrol on HepG2 cells and explored the underlying molecular mechanisms. Resveratrol inhibited proliferation and induced apoptosis in HepG2 cells via activation of caspase-9 and caspase-3, upregulation of the Bax/Bcl-2 ratio and induction of p53 expression. Cell cycle analysis demonstrated that resveratrol arrested cell cycle progression in the G1 and S phase. We further focused on the combination of matrine, a natural component extracted from the traditional Chinese medical herb Sophora flavescens Ait., as a mechanism to potentiate the growth-inhibitory effect of resveratrol on HepG2 cells. Both MTT and colony formation assay results indicated that the combined treatment of resveratrol and matrine exhibited a synergistic antiproliferative effect. In addition, resveratrol-induced apoptosis was significantly enhanced by matrine, which could be attributed to activation of caspase-3 and caspase-9, downregulation of survivin, induction of reactive oxygen species (ROS) generation and disruption of mitochondria membrane potential (Δψm). Our findings suggest that the combination treatment of resveratrol and matrine is a promising novel anticancer strategy for liver cancer; it also provides new insights into the mechanisms of combined therapy.
白藜芦醇是一种天然的多酚类植物化学物质，因其潜在的化学预防和化学治疗特性而受到广泛关注。在本研究中，我们首先评估了白藜芦醇对HepG2细胞的生长抑制作用，并探讨了其潜在的分子机制。白藜芦醇通过激活caspase-9和caspase-3、上调Bax/Bcl-2比值以及诱导p53表达来抑制HepG2细胞的增殖并诱导其凋亡。细胞周期分析表明，白藜芦醇使细胞周期进程停滞在G1期和S期。我们进一步关注了从传统中药苦参中提取的天然成分苦参碱，将其作为增强白藜芦醇对HepG2细胞生长抑制作用的一种机制。MTT和集落形成试验结果均表明，白藜芦醇与苦参碱联合处理具有协同抗增殖作用。此外，苦参碱显著增强了白藜芦醇诱导的凋亡，这可能归因于caspase-3和caspase-9的激活、生存素的下调、活性氧（ROS）生成的诱导以及线粒体膜电位（Δψm）的破坏。我们的研究结果表明，白藜芦醇与苦参碱联合治疗是一种有前景的新型肝癌抗癌策略；它也为联合治疗的机制提供了新的见解。
