Atractylon induces apoptosis and suppresses metastasis in hepatic cancer cells and inhibits growth in vivo
Atractylon induces apoptosis and suppresses metastasis in hepatic cancer cells and inhibits growth in vivo
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DOI：
10.2147/cmar.s194795
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Chen, Jianjie
中科院分区：
文献类型：
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作者：
Cheng, Yang;Chen, Tianyang;Chen, Jianjie
背景：肝癌是最常见的原发性肝脏恶性肿瘤，在世界范围内具有很高的发病率和死亡率。苍术龙是一种从苍术中分离得到的活性成分。直流。和苍术（苍术）Koidz。，它被证明有多种活动。方法：通过体外和体内实验对苍术龙的抗肝癌作用进行评价，并探讨其作用机制。细胞增殖、集落形成、细胞凋亡、迁移和侵袭，并通过MTT、结晶紫染色、流式细胞术分析和Transwell实验进行鉴定。用罗丹明123检测HepG2和MHCC97H细胞的δ Psi m。采用2,7-二氯二氢荧光素（DCFH-DA）法测定ROS水平。Western blot检测蛋白表达。通过皮下肿瘤模型评价白术龙体内抗肝癌的作用。结果：苍术龙对HepG2、SMCC7721、MHCC97H等肝癌细胞株具有明显的抑制增殖和促进凋亡的作用。此外，结果显示，苍术龙降低线粒体膜电位（Delta Psi m），增加ROS水平，抑制Bcl-2的表达，促进Bax和cleaved caspase-3的表达，表明苍术龙通过线粒体凋亡途径诱导HCC细胞凋亡。我们的研究结果还表明，苍术龙通过抑制上皮-间质转化（EMT）过程和下调MMP-2和MMP-9的表达来抑制肝癌细胞的迁移和侵袭。此外，苍术龙还能抑制肝癌的生长，并在体内对EMT过程有抑制作用。结论：综上所述，本研究提示苍术龙在体外具有抑制细胞增殖、诱导细胞凋亡、阻断侵袭、抑制体内生长等抗hcc作用。
Background: Hepatic cancer is the most common primary liver malignancy, with high incidence and mortality worldwide. Atractylon is an active constituent isolated from Atractylodes lancea (Thunb.) DC. and Atractylodes chinensis (DC.) Koidz., which proved to have multiple activities.Methods: 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 Delta Psi m of HepG2 and MHCC97H cells were detected by Rhodamine 123. The ROS level was determined by 2,7-Dichlorodihydrofluorescein 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.Results: 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 (Delta Psi m), 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.Conclusion: 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.