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.
PLoS One. 2013 Aug 12;8(8):e66751. doi: 10.1371/journal.pone.0066751. eCollection 2013.
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.
脑胶质瘤是原发性脑肿瘤中最具侵袭性的形式，因为它们倾向于侵犯周围健康的脑组织，从而使它们基本上无法治愈。水通道蛋白 AQP4 是维持中枢神经系统水和离子动态平衡的关键分子，除了其在脑水肿中的众所周知的功能外，最近有报道称它还与细胞存活有关。研究表明，多形性胶质母细胞瘤（GBM）中 AQP4 的表达增加，表明它也参与了恶性脑肿瘤的发生。在这项研究中，我们证明了 siRNA 介导的 AQP4 下调可诱导体外和体内脑胶质瘤细胞凋亡。我们进一步表明，几种凋亡关键蛋白，细胞色素 C、Bcl-2 和 Bad 参与了 AQP4 信号通路。我们的结果表明，AQP4 可能成为治疗脑胶质瘤的抗凋亡靶标。
