Department of Neurosurgery, The Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong, China.
Department of Neurosurgery, The Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong, China.
Biomed Pharmacother. 2018 Apr;100:358-366. doi: 10.1016/j.biopha.2018.02.006. Epub 2018 Feb 16.
Glioblastoma multiforme (GBM) is the most prevalent primary malignancy of the brain. This study was designed to investigate whether icaritin exerts anti-neoplastic activity against GBM in vitro.
Cell Counting Kit-8 (CCK-8) assay was utilized to examine the viability of GBM cells. The apoptotic cell population was measured by flow cytometry analysis. Cell cycle distribution was detected by flow cytometry as well. Western blot analysis was performed to examine the level of biomarker proteins in GBM cells. Levels of PPARγ mRNA and protein were detected by qPCR and western blot analysis, respectively. To examine the role of PPARγ in the anti-neoplastic activity of icaritin, PPARγ antagonist GW9662 or PPARγ siRNA was used. The activity of PPARγ was determined by DNA binding and luciferase assays.
Our findings revealed that icaritin markedly suppresses cell growth in a dose-dependent and time-dependent fashion. The cell population at the G0/G1 phase of the cell cycle was significantly increased following icaritin treatment. Meanwhile, icaritin promoted apoptotic cell death in T98G and U87MG cells. Further investigation showed upregulation of PPARγ played a key role in the anti-neoplastic activities of icaritin. Moreover, our result demonstrated activation of AMPK signaling by icaritin mediated the modulatory effect of icaritin on PPARγ.
Our results suggest the PPARγ may mediate anti-neoplastic activities against GBM.
多形性胶质母细胞瘤（GBM）是最常见的原发性脑恶性肿瘤。本研究旨在探讨淫羊藿素在体外对 GBM 是否具有抗肿瘤活性。
使用细胞计数试剂盒-8（CCK-8）检测 GBM 细胞活力。通过流式细胞术分析检测凋亡细胞群体。通过流式细胞术检测细胞周期分布。通过 Western blot 分析检测 GBM 细胞中生物标志物蛋白的水平。通过 qPCR 和 Western blot 分析分别检测 PPARγ mRNA 和蛋白的水平。为了研究 PPARγ 在淫羊藿素抗肿瘤活性中的作用，使用了 PPARγ 拮抗剂 GW9662 或 PPARγ siRNA。通过 DNA 结合和荧光素酶测定来检测 PPARγ 的活性。
我们的研究结果表明，淫羊藿素显著抑制细胞生长，呈剂量和时间依赖性。细胞周期 G0/G1 期的细胞群体在淫羊藿素处理后显著增加。同时，淫羊藿素促进 T98G 和 U87MG 细胞的凋亡细胞死亡。进一步的研究表明，PPARγ 的上调在淫羊藿素的抗肿瘤活性中起着关键作用。此外，我们的结果表明，淫羊藿素通过激活 AMPK 信号转导介导了对 PPARγ 的调节作用。
我们的结果表明，PPARγ 可能介导了对 GBM 的抗肿瘤活性。
