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Publications (2)5.64 Total impact

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    ABSTRACT: Malignant glioma is the most prevalent form of malignant brain tumor. Although radiotherapy is widely used in glioma treatment, the radioresistance of glioma cells limits the success of the glioma treatment. The lack of effective targets and signaling pathways to reverse glioma radioresistance is the critical obstacle in successful treatment. In this study, we demonstrate that mitochondrial ATP-sensitive potassium channels (mtKATP channels) are overexpressed in glioma cells and are closely related to the malignancy grade and the overall survival of the patients. Importantly, we showed that mtKATP channels could control glioma radioresistance by regulating reactive oxygen species (ROS)-induced ERK activation. The inhibition of mtKATP channels suppresses glioma radioresistance by inhibiting ERK activation both in vitro and in vivo. These findings reveal the important roles of the mitochondria and mtKATP channels as key regulators in the radioresistance of glioma cells, and suggest that mtKATP channel blockers and MAPK/ERK kinase (MEK) inhibitors are potential targets for drug development of glioma treatments.
    Molecular neurobiology. 09/2014;
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    ABSTRACT: Ion channels are found in a variety of cancer cells and necessary for cell cycle and cell proliferation. The roles of K(+) channels in the process are, however, poorly understood. In the present study, we report that adenosine triphosphate (ATP)-sensitive potassium channel activity plays a critical role in the proliferation of glioma cells. The expression of K(ATP) channels in glioma tissues was greatly increased than that in normal tissues. Treatment of glioma cells with tolbutamide, K(ATP) channels inhibitor, suppressed the proliferation of glioma cells and blocked glioma cell cycle in G(0)/G(1) phase. Similarly, downregulation of K(ATP) channels by small interfering RNA (siRNA) inhibited glioma cell proliferation. On the other hand, K(ATP) channels agonist diazoxide and overexpression of K(ATP) channels promoted the proliferation of glioma cells. Moreover, inhibiting K(ATP) channels slowed the formation of tumor in nude mice generated by injection of glioma cells. Whereas activating K(ATP) channels promoted development of tumor in vivo. The effect of K(ATP) channels activity on glioma cells proliferation is mediated by extracellular signal-regulated kinase (ERK) activation. We found that activating K(ATP) channel triggered ERK activation and inhibiting K(ATP) channel depressed ERK activation. U-0126, the mitogen-activated protein kinase kinase (MAPK kinase) inhibitors blocked ERK activation and cell proliferation induced by diazoxide. Furthermore, constitutively activated MEK plasmids transfection reversed the inhibitory effects of tolbutamide on glioma proliferation, lending further support for a role of ERK in mediating this process. Our results suggest that K(ATP) channels control glioma cell proliferation via regulating ERK pathway. We concluded that K(ATP) channels are important in pathological cell proliferation and open a promising pathway for novel targeted therapies.
    Carcinogenesis 02/2009; 30(5):737-44. · 5.64 Impact Factor