Expression of Cytosolic Phospholipase A2 Alpha in Glioblastoma Is Associated With Resistance to Chemotherapy

Abstract

BackgroundThe clinical management of glioblastoma is still challenging despite aggressive surgery and radio-chemotherapy approaches. Better understanding of the molecules involved in glioblastoma chemoresistance is necessary to improve the treatment and predict prognosis. Materials and MethodsWe analyzed the expression and possible roles of cytosolic phospholipase A2 alpha (cPLA2α) in human glioblastoma cell lines and patient samples using immunohistochemistry and cellular assays. We analyzed the signaling pathways that cPLA2α regulates in glioblastoma cells using western blot analysis. ResultsOur work demonstrated that cPLA2α is upregulated in glioblastoma compared with normal neuron cells. The expression of cPLA2α varies in multiple glioblastoma cell lines and is associated with chemoresistance rather than tumor development. cPLA2α depletion moderately inhibits glioblastoma growth and survival but remarkably sensitizes chemo-resistant glioblastoma cells to several chemotherapeutic agents. Mechanistically, cPLA2α knockdown significantly suppresses the PI3K/Akt/mTOR pathway in glioblastoma cells. ConclusionsWe are the first to identify the important role of cPLA2α in glioblastoma in response to chemotherapy. Our data also suggest that cPLA2α may serve as a biomarker to indicate prognosis of glioblastoma patients with high level of cPLA2α to chemotherapy.