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Ion channels in pediatric CNS Atypical Teratoid/Rhabdoid Tumor (AT/RT) cells: potential targets for novel therapeutic agents
被引:2
作者:
Banderali, Umberto
[1
]
Jayanthan, Aarthi
[2
]
Hoeksema, Kimberley A.
[2
]
Narendran, Aru
[2
]
Giles, Wayne R.
[1
]
机构:
[1] Univ Calgary, Fac Kinesiol, Calgary, AB T2N 1N4, Canada
[2] Univ Calgary, Fac Med, Alberta Childrens Hosp, Div Pediat Oncol, Calgary, AB T2N 1N4, Canada
关键词:
Atypical Teratoid/Rhabdoid Tumor;
Chloride channels;
Volume regulation;
Cell proliferation;
Cancer drugs;
SENSITIVE CHLORIDE CHANNELS;
VOLUME REGULATION;
EPITHELIAL-CELLS;
CL-CHANNELS;
CANCER;
PROLIFERATION;
CONDUCTANCE;
APOPTOSIS;
BLOCKADE;
CYCLE;
D O I:
10.1007/s11060-011-0735-x
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
The central nervous system Atypical Teratoid/Rhabdoid Tumor (CNS AT/RT) is a highly malignant neoplasm that commonly affects infants and young children, and has an extremely poor prognosis. Recently, a small subset of ion channels have been found to be over-expressed in a variety of malignant cells, thus emerging as potential therapeutic targets for difficult to treat tumors. We have studied the electrophysiological properties of AT/RT cell lines with particular attention to cell volume sensitive ion channels (VSC). This class of membrane proteins can play a fundamental role in cellular processes relevant to tumor development. We have found that chloride selective VSCs are particularly active in AT/RT cell lines, compared to non-tumor cells. We evaluated specific inhibitors for activity against chloride selective VSCs and consequently for their ability to inhibit the growth and survival of AT/RT cells in vitro. The results demonstrated that the extent of volume sensitive membrane current inhibition by these agents was correlated with their potency in AT/RT cell growth inhibition in vitro. In addition, we showed that ion channel inhibition enhanced the activity of certain anti-neoplastic agents, suggesting its value in effective drug combination protocols. Results presented provide preliminary in vitro data for possible evaluation of distinct ion channels as plausible therapeutic targets in the treatment of AT/RT.
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页码:111 / 119
页数:9
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