Haris Khalilah, Ismail Samhani, Idris Zamzuri, Abdullah Jafri Malin, Yusoff Abdul Aziz Mohamed
Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia E-mail :
Asian Pac J Cancer Prev. 2014;15(11):4499-505. doi: 10.7314/apjcp.2014.15.11.4499.
Glioblastoma, the most aggressive and malignant form of glioma, appears to be resistant to various chemotherapeutic agents. Hence, approaches have been intensively investigated to targeti specific molecular pathways involved in glioblastoma development and progression. Aloe emodin is believed to modulate the expression of several genes in cancer cells. We aimed to understand the molecular mechanisms underlying the therapeutic effect of Aloe emodin on gene expression profiles in the human U87 glioblastoma cell line utilizing microarray technology. The gene expression analysis revealed that a total of 8,226 gene alterations out of 28,869 genes were detected after treatment with 58.6 μg/ml for 24 hours. Out of this total, 34 genes demonstrated statistically significant change (p<0.05) ranging from 1.07 to 1.87 fold. The results revealed that 22 genes were up-regulated and 12 genes were down-regulated in response to Aloe emodin treatment. These genes were then grouped into several clusters based on their biological functions, revealing induction of expression of genes involved in apoptosis (programmed cell death) and tissue remodelling in U87 cells (p<0.01). Several genes with significant changes of the expression level e.g. SHARPIN, BCAP31, FIS1, RAC1 and TGM2 from the apoptotic cluster were confirmed by quantitative real-time PCR (qRT-PCR). These results could serve as guidance for further studies in order to discover molecular targets for the cancer therapy based on Aloe emodin treatment.
胶质母细胞瘤是胶质瘤中最具侵袭性和恶性的形式，似乎对各种化疗药物具有抗性。因此，针对参与胶质母细胞瘤发生和发展的特定分子途径的方法已被深入研究。芦荟大黄素被认为可调节癌细胞中几种基因的表达。我们旨在利用微阵列技术了解芦荟大黄素对人U87胶质母细胞瘤细胞系基因表达谱治疗作用的分子机制。基因表达分析显示，在用58.6μg/ml处理24小时后，在28,869个基因中总共检测到8,226个基因改变。在这总数中，34个基因显示出统计学上的显著变化（p<0.05），变化范围为1.07至1.87倍。结果显示，响应芦荟大黄素处理，22个基因上调，12个基因下调。然后根据它们的生物学功能将这些基因分为几个簇，揭示U87细胞中参与凋亡（程序性细胞死亡）和组织重塑的基因表达的诱导（p<0.01）。通过定量实时PCR（qRT-PCR）证实了凋亡簇中表达水平有显著变化的几个基因，例如SHARPIN、BCAP31、FIS1、RAC1和TGM2。这些结果可为进一步研究提供指导，以便发现基于芦荟大黄素治疗的癌症治疗的分子靶点。
