Knockdown a water channel protein, aquaporin-4, induced glioblastoma cell apoptosis

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 sy...

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Bibliographic Details
Published in:PloS one 2013-08, Vol.8 (8), p.e66751
Main Authors: Ding, Ting, Zhou, Ying, Sun, Kai, Jiang, Weizhong, Li, Wenliang, Liu, Xiaoli, Tian, Chunying, Li, Zhihui, Ying, Guoguang, Fu, Li, Gu, Feng, Li, Weidong, Ma, Yongjie
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - drug effects
Apoptosis - genetics
Aquaporin 4
Aquaporin 4 - genetics
Aquaporins
B cells
Bcl-2 protein
Biology
Brain
Brain cancer
Brain Neoplasms - genetics
Brain Neoplasms - pathology
Brain tumors
Breast cancer
Cell Line, Tumor
Cell survival
Central nervous system
Cytochrome
Cytochrome c
Disease prevention
Edema
Education
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Gene therapy
Glioblastoma
Glioblastoma - genetics
Glioblastoma - pathology
Glioblastoma multiforme
Glioblastomas
Homeostasis
Hospitals
Humans
Kinases
Laboratories
Male
Medicine
Mice
Permeability
Proteins
RNA Interference
Rodents
Signaling
siRNA
Stem cells
Tetradecanoylphorbol Acetate - pharmacology
Tissues
Tumors
Xenograft Model Antitumor Assays
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0066751