Effect of CAL-101 on gene regulation of phosphoinositol 3-kinase isoform p110δ in the pathogenesis of glioblastoma multiforme

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Effect of CAL-101 on gene regulation of phosphoinositol 3-kinase isoform p110δ in the pathogenesis of glioblastoma multiforme

 

Author: Chan, Kam Hung Beny
Title: Effect of CAL-101 on gene regulation of phosphoinositol 3-kinase isoform p110δ in the pathogenesis of glioblastoma multiforme
Degree: M.Sc.
Year: 2013
Subject: Phosphoinositides.
Gliomas -- Treatment.
Glioblastoma multiforme
Hong Kong Polytechnic University -- Dissertations
Department: Dept. of Health Technology and Informatics
Pages: xii, 79 leaves : ill. (some col.) ; 30 cm.
Language: English
InnoPac Record: http://library.polyu.edu.hk/record=b2637220
URI: http://theses.lib.polyu.edu.hk/handle/200/7060
Abstract: Glioblastoma multiforme (GBM) is the most highly invasive malignant brain tumor in humans. It is classified as Grade IV astrocytoma in accordance with the World Health Organization (WHO). Since GBM tumors are characterized by highly invasive and diffuse growth, surgical control of the disease is impossible. The standard treatment of GBM is ineffective with recurrent GBM due to the migration and insidious invasion abilities of glioma cells. In recent research, PI3K/ Akt signaling pathway is believed to mediate the proliferation, apoptosis, migration and invasion of glioma cells. Knockdown of p110δ reduces the migration and invasion ability of glioma cells in GBM. U87 human malignant glioblastoma cell line is used for analysis in this study in order to identify genes involved in migration and invasion of glioma cells. This cell line expresses all class IA PI3K isoforms and is well-characterized with PTEN-deficient status. U87MG cells were treated with different concentrations of CAL-101 with DMSO as carrier control. Total protein was analyzed for p110δ, phospho-Akt (Ser⁴⁷³), phospho-Akt (Thr³⁰⁸), total Akt and β-actin, in order to identify the optimal concentration of CAL-101 with reduced protein expression of phospho-Akt. Gene expression in treated cells and carrier control cells were analyzed with extracellular matrix and adhesion molecules 96 well plates by PCR array using the Real-Time 7500 PCR system. Relative quantification of individual gene was analyzed by DataAssist software. Level of gene expression was expressed with fold change ((2^(-ΔΔCt)) according to the cycle threshold (Ct) values of the genes. It was revealed that gene for ADAMTS1 was up-regulated with fold change of 2.7, while COL11A1 gene was down-regulated with fold change of 3.0 after treatment with 5 μM CAL-101 for 24 hours. Genes of downstream pathways could be significantly affected by the activity of p110δ. Isoform-specific inhibitor may be a better way to treat glioma patients, for efficient control of glioma cell migration and invasion.

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