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 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.
Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Breast Cancer Prevention and Therapy of the Ministry of Education, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin, China.
Ting
T
Ding
Ying
Y
Zhou
Kai
K
Sun
Weizhong
W
Jiang
Wenliang
W
Li
Xiaoli
X
Liu
Chunying
C
Tian
Zhihui
Z
Li
Guoguang
G
Ying
Li
L
Fu
Feng
F
Gu
Weidong
W
Li
Yongjie
Y
Ma
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D051401:Aquaporin 4 / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D034622:RNA Interference; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D051401:Aquaporin 4; D013755:Tetradecanoylphorbol Acetate