Stump Trevor A, Santee Brittany N, Williams Lauren P, Kunze Rachel A, Heinze Chelsae E, Huseman Eric D, Gryka Rebecca J, Simpson Denise S, Amos Samson
Department of Pharmaceutical Sciences, School of Pharmacy, Health Sciences Center, Cedarville University, Cedarville, OH, USA.
J Pharm Pharmacol. 2017 Jul;69(7):907-916. doi: 10.1111/jphp.12718. Epub 2017 Mar 28.
Glioblastoma (GBM) is highly proliferative, infiltrative, malignant and the most deadly form of brain tumour. The epidermal growth factor receptor (EGFR) is overexpressed, amplified and mutated in GBM and has been shown to play key and important roles in the proliferation, growth and survival of this tumour. The goal of our study was to investigate the antiproliferative, apoptotic and molecular effects of apigenin in GBM.
Proliferation and viability tests were carried out using the trypan blue exclusion, MTT and lactate dehydrogenase (LDH) assays. Flow cytometry was used to examine the effects of apigenin on the cell cycle check-points. In addition, we determined the effects of apigenin on EGFR-mediated signalling pathways by Western blot analyses.
Our results showed that apigenin reduced cell viability and proliferation in a dose- and time-dependent manner while increasing cytotoxicity in GBM cells. Treatment with apigenin-induced is poly ADP-ribose polymerase (PARP) cleavage and caused cell cycle arrest at the G2M checkpoint. Furthermore, our data revealed that apigenin inhibited EGFR-mediated phosphorylation of mitogen-activated protein kinase (MAPK), AKT and mammalian target of rapamycin (mTOR) signalling pathways and attenuated the expression of Bcl-xL.
Our results demonstrated that apigenin has potent inhibitory effects on pathways involved in GBM proliferation and survival and could potentially be used as a therapeutic agent for GBM.
胶质母细胞瘤（GBM）具有高度增殖性、浸润性、恶性，是最致命的脑肿瘤形式。表皮生长因子受体（EGFR）在GBM中过度表达、扩增和突变，已证明在该肿瘤的增殖、生长和存活中起关键重要作用。我们研究的目的是探讨芹菜素对GBM的抗增殖、凋亡和分子效应。
使用台盼蓝排斥法、MTT法和乳酸脱氢酶（LDH）测定法进行增殖和活力测试。采用流式细胞术检测芹菜素对细胞周期检查点的影响。此外，我们通过蛋白质印迹分析确定芹菜素对EGFR介导的信号通路的影响。
我们的结果表明，芹菜素以剂量和时间依赖性方式降低细胞活力和增殖，同时增加GBM细胞的细胞毒性。芹菜素处理诱导多聚ADP核糖聚合酶（PARP）裂解，并导致细胞周期在G2M检查点停滞。此外，我们的数据显示芹菜素抑制EGFR介导的丝裂原活化蛋白激酶（MAPK）、AKT和雷帕霉素哺乳动物靶标（mTOR）信号通路的磷酸化，并减弱Bcl-xL的表达。
我们的结果表明，芹菜素对参与GBM增殖和存活的通路具有强大的抑制作用，有可能用作GBM的治疗剂。
