Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 China.
Cancer Cell Int. 2015 Feb 4;15(1):12. doi: 10.1186/s12935-015-0160-x. eCollection 2015.
Malignant glioma is the most devastating and aggressive tumour in the brain and is characterised by high morbidity, high mortality and extremely poor prognosis. The main purpose of the present study was to investigate the effects of schisandrin B (Sch B) on glioma cells both in vitro and in vivo and to explore the possible anticancer mechanism underlying Sch B-induced apoptosis and cell cycle arrest.
The anti-proliferative ability of Sch B on glioma cells were assessed by MTT and clony formation assays. Flow cytometric analysis was used to detect cell cycle changes. Apoptosis was determined by Hoechst 33342 staining and annexin V/PI double-staining assays. The mitochondrial membrane potential was detected by Rhodamine 123 staining. The in vivo efficacy of Sch B was measured using a U87 xenograft model in nude mice. The expressions of the apoptosis-related and cell cycle-related proteins were analysed by western blot. Student's t-test was used to compare differences between treated groups and their controls.
We found that Sch B inhibited growth in a dose- and time-dependent manner as assessed by MTT assay. In U87 and U251 cells, the number of clones was strongly suppressed by Sch B. Flow cytometric analysis revealed that Sch B induced cell cycle arrest in glioma cells at the G0/G1 phase. In addition, Sch B induced glioma cell apoptosis and reduced mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Mechanically, western blot analysis indicated that Sch B induced apoptosis by caspase-3, caspase-9, PARP, and Bcl-2 activation. Moreover, Sch B significantly inhibited tumour growth in vivo following the subcutaneous inoculation of U87 cells in athymic nude mice.
In summary, Sch B can reduce cell proliferation and induce apoptosis in glioma cells and has potential as a novel anti-tumour therapy to treat gliomas.
恶性脑胶质瘤是大脑中最具破坏性和侵袭性的肿瘤，其发病率高、死亡率高、预后极差。本研究的主要目的是研究五味子乙素（Sch B）在体外和体内对神经胶质瘤细胞的作用，并探讨 Sch B 诱导细胞凋亡和细胞周期阻滞的潜在抗癌机制。
通过 MTT 和集落形成实验评估 Sch B 对神经胶质瘤细胞的增殖抑制作用。采用流式细胞术分析检测细胞周期变化。通过 Hoechst 33342 染色和 Annexin V/PI 双染法检测细胞凋亡。通过 Rhodamine 123 染色检测线粒体膜电位。采用 U87 移植瘤模型在裸鼠体内评估 Sch B 的体内疗效。通过 Western blot 分析检测凋亡相关和细胞周期相关蛋白的表达。采用 Student's t 检验比较实验组与对照组之间的差异。
我们发现 Sch B 通过 MTT 测定以剂量和时间依赖性方式抑制生长。在 U87 和 U251 细胞中，Sch B 强烈抑制克隆形成。流式细胞术分析显示 Sch B 诱导神经胶质瘤细胞在 G0/G1 期发生细胞周期阻滞。此外，Sch B 以剂量依赖性方式诱导神经胶质瘤细胞凋亡并降低线粒体膜电位（ΔΨm）。机制上，Western blot 分析表明 Sch B 通过 caspase-3、caspase-9、PARP 和 Bcl-2 的激活诱导细胞凋亡。此外，Sch B 明显抑制了荷瘤裸鼠皮下接种 U87 细胞后的肿瘤生长。
总之，Sch B 可减少神经胶质瘤细胞的增殖并诱导其凋亡，具有作为治疗神经胶质瘤的新型抗肿瘤治疗的潜力。
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