Wang Rong, Deng Danni, Shao Naiyuan, Xu Yuan, Xue Lian, Peng Ya, Liu Yatian, Zhi Feng
Department of Neurosurgery, The First People's Hospital of Changzhou, Changzhou, Jiangsu, China.
Modern Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
Onco Targets Ther. 2018 Mar 2;11:1183-1192. doi: 10.2147/OTT.S155275. eCollection 2018.
Glioblastoma multiforme (GBM) is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis. No further improvements in outcomes have been reported since radiotherapy-temozolomide therapy was introduced. Therefore, developing new agents to treat GBM is important.
This study aimed to evaluate the anti-tumor effect of evodiamine (Evo) on GBM cells, and to determine the underlying mechanisms involved.
According to MTT assay results, Evo significantly inhibited the cell proliferation in a time- and dose-dependent manner. Fluorescence microscopy and flow cytometry analyses revealed that Evo induced cell apoptosis in a concentration-dependent manner. Moreover, Evo induced reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) disruption. Finally, Evo induced apoptosis in cancer cells by suppressing PI3K/AKT signaling and inducing MAPK phosphorylation (p38 and JNK, but not ERK) to regulate apoptotic proteins (Bax, Bcl-2, Cytochrome c, Caspase-3, and PARP).
In summary, Evo inhibits cell proliferation by inducing cellular apoptosis via suppressing PI3K/AKT and activating MAPK in GBM; these results indicate that Evo may be regarded as a new approach for GBM treatment.
多形性胶质母细胞瘤（GBM）是中枢神经系统最恶性的原发性肿瘤，预后很差。自从引入放疗-替莫唑胺疗法以来，尚未有关于疗效进一步改善的报道。因此，开发治疗GBM的新药物很重要。
本研究旨在评估吴茱萸碱（Evo）对GBM细胞的抗肿瘤作用，并确定其潜在机制。
根据MTT试验结果，Evo以时间和剂量依赖性方式显著抑制细胞增殖。荧光显微镜和流式细胞术分析显示，Evo以浓度依赖性方式诱导细胞凋亡。此外，Evo诱导活性氧（ROS）产生和线粒体膜电位（MMP）破坏。最后，Evo通过抑制PI3K/AKT信号传导并诱导MAPK磷酸化（p38和JNK，但不包括ERK）来调节凋亡蛋白（Bax、Bcl-2、细胞色素c、Caspase-3和PARP），从而诱导癌细胞凋亡。
总之，Evo通过在GBM中抑制PI3K/AKT并激活MAPK来诱导细胞凋亡，从而抑制细胞增殖；这些结果表明Evo可被视为一种治疗GBM的新方法。
