Targeting inhibitory kappa B kinase alpha (IKKα) signalling in glioblastoma

Student thesis: Doctoral Thesis

Abstract

Introduction: Cancer is a broad term, which covers a number of conditions characterised by uncontrolled cellular proliferation mainly due to genetic mutations. One of the most aggressive types of cancer is Glioblastoma multiforme (GBM). Presently, glioblastoma is considered an incurable type of cancer. Therefore, scientists are studying new patterns and mechanisms to supress GBM; one of which is through interrupting specific signalling pathways in tumour cells. One of the prominent pathways driving the tumour cell signalling responses and showing significant effects on cancer hallmarks, is the Nuclear Factor Kappa-B (NF-κB) pathway. Aim: The aim of the study is to investigate the pharmacological effect of selective IKKα inhibitors through examining their selectivity within both the non-canonical and canonical NF-κBpathways and their effect on IKKα-dependent cellular processes that underpin the phenotypic outcomes that support GBM development. Methods: Western Blotting was pursued with both whole cell extracts and crude nuclear extracts to determine the expression/phosphorylation/localisation of key signalling proteins. EMSA was used to determine the protein-DNA binding activity while MTT assay and clonogenic assay were used to identify cellular viability and clonogenic survival, respectively. All data shown were expressed as mean ± S.E.M. Statistical analysis was performed using GraphPad Prism version 10.1.0. The statistical significance of differences between mean values from control and treated groups were determined by one-way analysis of variance (ANOVA) with Dunnett’s post-test (p
Date of Award16 May 2024
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorAndrew Paul (Supervisor) & Marie Boyd (Supervisor)

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