期刊
CANCER LETTERS
卷 282, 期 1, 页码 35-42出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2009.02.055
关键词
Pentobarbital; Malignant glioma; Proliferation; Migration; Cell cycle; MAPK
类别
资金
- National Natural Science Foundation of China [30830111, 330801408]
- National Natural Science Foundation of Guangdong Province [8451008901000297]
Malignant gliomas are common and aggressive brain tumors in adults. The rapid proliferation and diffuse brain migration are main obstacles to successful treatment. Here we show that pentobarbital, a central depressant introduced clinically a century ago, is capable of suppressing proliferation and migration of C6 malignant glioma cells in a concentration-dependent manner. Pentobarbital also leads to a G1 phase cell cycle arrest accompanied by suppressed G1 cell cycle regulatory proteins Cyclin D1, Cyclin D3, CDK2 and phosphorylated Rb. In addition, noticeable morphological changes and interrupted alpha-tubulin microtubule assembly are induced by pentobarbital exposure. Intracellular signal pathways involved in the effect of pentobarbital is concerned with inactivation of ERK, c-Jun and Akt. Together, these findings suggest anti-proliferation and anti-migration effects of pentobarbital on malignant gliomas, most likely by arresting cell cycle and interfering microtubule. ERK, c-Jun MAPK and PI3K/Akt are possible signaling pathways involved. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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