Yang Fan, Shi Le, Liang Tao, Ji Leilei, Zhang Guangji, Shen Yang, Zhu Fangfang, Xu Li
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
Biochem Biophys Res Commun. 2017 Mar 25;485(1):54-61. doi: 10.1016/j.bbrc.2017.02.017. Epub 2017 Feb 9.
Evodiamine is an alkaloid extracted from Euodia rutaecarpa (Juss.) Benth. There is little information about the mechanisms of evodiamine on the apoptosis of hepatocellular carcinoma (HCC).
A xenograft model and CCK8 assay were used to investigate the anti-HCC effect of evodiamine. The effect of evodiamine on apoptosis was evaluated by DAPI staining and flow cytometry. Western blot analyses and immunohistochemistry were processed to assess the protein expressions of Akt and apoptotic proteins.
Evodiamine suppressed tumor growth, improved the expression of cleaved-caspase3 and decreased tumor specific growth factor (TSGF) and alpha fetoprotein (AFP) activities. Furthermore, evodiamine inhibited cell viability and induced cell cycle arrest. DAPI staining revealed nuclear condensation in evodiamine-treated groups. Meanwhile, evodiamine increased the number of apoptotic cells. Furthermore, evodiamine suppressed Akt and regulated apoptotic proteins in HepG2 cells. Evodiamine decreased p-Akt levels activated by SC79, which led to the increase of bax/bcl-2 and cleaved-caspase3.
Our findings suggested that evodiamine could exert anti-HCC effect through inducing Akt-mediated apoptosis. Evodiamine has the potential to be a therapeutic medicine for HCCs.
吴茱萸碱是从吴茱萸中提取的一种生物碱。关于吴茱萸碱对肝细胞癌（HCC）凋亡机制的信息较少。
采用异种移植模型和CCK8测定法研究吴茱萸碱的抗肝癌作用。通过DAPI染色和流式细胞术评估吴茱萸碱对凋亡的影响。进行蛋白质免疫印迹分析和免疫组织化学以评估Akt和凋亡蛋白的表达。
吴茱萸碱抑制肿瘤生长，提高裂解型半胱天冬酶3的表达，并降低肿瘤特异性生长因子（TSGF）和甲胎蛋白（AFP）活性。此外，吴茱萸碱抑制细胞活力并诱导细胞周期停滞。DAPI染色显示吴茱萸碱处理组出现核浓缩。同时，吴茱萸碱增加凋亡细胞数量。此外，吴茱萸碱抑制HepG2细胞中的Akt并调节凋亡蛋白。吴茱萸碱降低了由SC79激活的p-Akt水平，导致bax/bcl-2和裂解型半胱天冬酶3增加。
我们的研究结果表明，吴茱萸碱可通过诱导Akt介导的凋亡发挥抗肝癌作用。吴茱萸碱有潜力成为肝癌的治疗药物。
