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INVESTIGATING THE ROLE THE PI3K PATHWAY PLAYS IN EPENDYMOMA PATHOGENESIS Free

INTRODUCTION: The PI3K pathway has been implicated in cancer development as it is central in facilitating cell survival and viability. We have recently shown that the pathway was activated in ependymoma, the second most common malignant paediatric brain tumour. We therefore treated ependymoma cell lines with BKM120, a pan-PI3K inhibitor, to elucidate downstream mechanisms that would potentially drive ependymoma pathogenesis. METHOD: We evaluated the extent of BKM120-mediated inhibition of the PI3K and mTOR signalling pathways in our panel of ependymoma cell lines through Western Blot. Apoptotic assays were performed to establish the functional relevance of the PI3K pathway in ependymoma. A combination of computational and experimental techniques was also used to characterise the downstream events affected by the pathway's activation. RESULTS: Results showed that BKM120 reduced the intracellular levels of p-AKT, which confirms the inhibition of the PI3K pathway. Phosphorylation of S6 was also found to be inhibited, which suggests that the PI3K/AKT/mTOR axis is active in these cell lines. MTT assays indicated a decrease in cell viability and apoptotic assays are ongoing to clarify whether this is due to cell death or growth inhibition. CONCLUSION: Up-regulation of mTOR signalling through the activation of the PI3K pathway may be contributory to ependymoma pathogenesis. Our data therefore suggests the potential benefits of using PI3K/mTOR dual inhibitors to treat ependymoma. Determining other downstream targets is essential in order to fully understand the role of the PI3K pathway in ependymoma development and facilitate the identification of novel targets to maximise chemotherapeutic efficiency.