Cheng Yang, Chen Tianyang, Yang Xueli, Xue Jianhua, Chen Jianjie
Department of Liver Disease, Hospital for Infectious Diseases of Pudong District, Shanghai 201299, People's Republic of China.
Institute of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People's Republic of China.
Cancer Manag Res. 2019 Jun 28;11:5883-5894. doi: 10.2147/CMAR.S194795. eCollection 2019.
Hepatic cancer is the most common primary liver malignancy, with high incidence and mortality worldwide. Atractylon is an active constituent isolated from (Thunb.) DC. and (DC.) Koidz., which proved to have multiple activities. In this study, we evaluated the antihepatic cancer (HCC) effect of atractylon in vitro and in vivo and investigated its underlying mechanism. Cell proliferation, colony formation, cell apoptosis, migration and invaison and was identified by MTT, crystal violet staining, flow cytometry analysis, and Transwell assay. The ∆Ψm of HepG2 and MHCC97H cells were detected by Rhodamine 123. The ROS level was determined by 2,7-Dichlorodi-hydrofluorescein diacetate (DCFH-DA) method. Protein expression was identified by Western blot analysis. The anti-HCC effect of atractylon in vivo was evaluated by a subcutaneous tumor model. The results suggested that atractylon significantly inhibits the proliferation and promotes apoptosis of hepatic cancer cell lines, including HepG2, SMCC7721, and MHCC97H. Moreover, the results showed that atractylon reduces the mitochondrial membrane potential (∆Ψm), increases ROS level, inhibits the expression of Bcl-2, and promotes the expression of Bax and cleaved caspase-3, indicating that atractylon induces HCC apoptosis through the mitochondrial apoptotic pathway. Our results also demonstrated that atractylon inhibits migration and invasion of hepatic cancer cells by inhibiting the epithelial-mesenchymal transition (EMT) process and downregulating MMP-2 and MMP-9 expression. In addition, atractylon inhibited the growth of hepatic cancer and showed an inhibition effect on EMT process in vivo. In all, this study suggested that atractylon showed a promising anti-HCC effect with inhibiting proliferation, inducing apoptosis, and blocking invasion in vitro and inhibiting growth in vivo.
肝癌是最常见的原发性肝脏恶性肿瘤，在全球范围内发病率和死亡率都很高。苍术酮是从白术（Thunb.）DC.和关苍术（DC.）Koidz.中分离出的一种活性成分，已被证明具有多种活性。在本研究中，我们评估了苍术酮在体外和体内对肝癌（HCC）的抗癌作用，并研究了其潜在机制。通过MTT、结晶紫染色、流式细胞术分析和Transwell试验鉴定细胞增殖、集落形成、细胞凋亡、迁移和侵袭。用罗丹明123检测HepG2和MHCC97H细胞的线粒体膜电位（∆Ψm）。用2,7-二氯二氢荧光素二乙酸酯（DCFH-DA）法测定活性氧（ROS）水平。通过蛋白质印迹分析鉴定蛋白质表达。通过皮下肿瘤模型评估苍术酮在体内的抗肝癌作用。结果表明，苍术酮显著抑制肝癌细胞系（包括HepG2、SMCC7721和MHCC97H）的增殖并促进其凋亡。此外，结果显示苍术酮降低线粒体膜电位（∆Ψm），增加ROS水平，抑制Bcl-2的表达，并促进Bax和裂解的caspase-3的表达，表明苍术酮通过线粒体凋亡途径诱导肝癌细胞凋亡。我们的结果还表明，苍术酮通过抑制上皮-间质转化（EMT）过程并下调MMP-2和MMP-9的表达来抑制肝癌细胞的迁移和侵袭。此外，苍术酮在体内抑制肝癌生长并对EMT过程显示出抑制作用。总之，本研究表明苍术酮在体外具有抑制增殖、诱导凋亡和阻断侵袭以及在体内抑制生长的有前景的抗肝癌作用。
