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

Ting Ding; Ying Zhou; Kai Sun; Weizhong Jiang; Wenliang Li; Xiaoli Liu; Chunying Tian; Zhihui Li; Guoguang Ying; Li Fu; Feng Gu; Weidong Li; Yongjie Ma

doi:10.1371/journal.pone.0066751

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

PLoS One. 2013 Aug 12;8(8):e66751. doi: 10.1371/journal.pone.0066751. eCollection 2013.

Authors

Ting Ding¹, Ying Zhou, Kai Sun, Weizhong Jiang, Wenliang Li, Xiaoli Liu, Chunying Tian, Zhihui Li, Guoguang Ying, Li Fu, Feng Gu, Weidong Li, Yongjie Ma

Affiliation

¹ 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Apoptosis / genetics*
Aquaporin 4 / genetics*
Brain Neoplasms / genetics*
Brain Neoplasms / pathology
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Glioblastoma / genetics*
Glioblastoma / pathology
Humans
Male
Mice
RNA Interference
Tetradecanoylphorbol Acetate / pharmacology
Xenograft Model Antitumor Assays

Substances

Aquaporin 4
Tetradecanoylphorbol Acetate

Grants and funding

This study was supported by the China 973 project (2009CB521705, 2010CB529405, 2010CB529604), the National Scientific Foundation of China (81072158, 81272358, 81271511), the Key Program of the National Scientific Foundation of China (30930038), the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, “Shu Guang” project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (10SG14) and the Pujiang Program of Shanghai (11PJ1405100). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.