Abstract
Glioblastomas are the most aggressive forms of primary brain tumors due to their tendency to invade surrounding healthy brain tissues, rendering them largely incurable. The water channel protein, Aquaporin-4 (AQP4) is a key molecule for maintaining water and ion homeostasis in the central nervous system and has recently been reported with cell survival except for its well-known function in brain edema. An increased AQP4 expression has been demonstrated in glioblastoma multiforme (GBM), suggesting it is also involved in malignant brain tumors. In this study, we show that siRNA-mediated down regulation of AQP4 induced glioblastoma cell apoptosis in vitro and in vivo. We further show that several apoptotic key proteins, Cytochrome C, Bcl-2 and Bad are involved in AQP4 signaling pathways. Our results indicate that AQP4 may serve as an anti-apoptosis target for therapy of glioblastoma.
Highlights
Glioblastoma has a high proliferation ability and high tendency to invade diffusely into surrounding healthy brain tissues, thereby precluding their successful surgical removal [1,2]
We show that down-regulation of AQP4 using a specific siRNA or an inhibitor, phorbol 12-myristate 13-acetate (PMA), induced apoptosis and impaired the proliferation of the LN229 and U87 Human glioblastoma cell lines
Cell culture and reagents Human glioblastoma cell lines LN229 and U87 were obtained from American Type Culture Collection (Manassas, VA, USA) and were cultured in Roswell Park Memorial Institute (RPMI) 1640 medium containing with 10% Fetal Bovine Serum (FBS)
Summary
Glioblastoma has a high proliferation ability and high tendency to invade diffusely into surrounding healthy brain tissues, thereby precluding their successful surgical removal [1,2]. 13 different AQPs (AQP 0–12) have been identified in mammals These integral proteins have been found to form transmembrane water channels that play critical roles in controlling the water flow into and out of cells [3]. AQP4 is primarily expressed at the border between brain parenchyma and major fluid compartments, including astrocyte foot processes, glia limitans, as well as ependymal cells and subependymal astrocytes [5]. This distribution suggests that AQP4 control water fluxes into and out of the brain parenchyma
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