机构：[1]The Special Procurement Ward & Department of Neurology, the Second Affiliated Hospital of Soochow University, Suzhou, China,[2]Institute of Neuroscience, Soochow University, Suzhou, China,[3]Department of Neurobiology and Medical Psychology, Medical College of Soochow University, Suzhou, China
BACKGROUND AND PURPOSE Endostatin (ES) is a c-terminal proteolytic fragment of collagen XVIII with promising antitumour properties in several tumour models, including human glioblastoma. We hypothesized that this peptide could interact with plasma membrane ion channels and modulate their functions. EXPERIMENTAL APPROACH Using cell proliferation and migration assays, patch clamp and Western blot analysis, we studied the effects of ES on the proliferation and migration of human glioblastoma U87 cells, mediated by T-type Ca2+ channels. KEY RESULTS Extracellular application of ES reversibly inhibited T-type Ca2+ channel currents (T-currents) in U87 cells, whereas L-type Ca2+ currents were not affected. This inhibitory effect was associated with a hyperpolarizing shift in the voltage-dependence of inactivation but was independent of G-protein and protein tyrosine kinase-mediated pathways. All three a1 subunits of T-type Ca2+ channels (CaV3), a1G (CaV3.1), a1H (CaV3.2) and a1I (CaV3.3), were endogenously expressed in U87 cells. Using transfected HEK293 or CHO cells, we showed that only CaV3.1 and CaV3.2, but not CaV3.3 or CaV1.2 (L-type), channel currents were significantly inhibited. More interestingly, ES inhibited the proliferation and migration of U87 cells in a dose-dependent manner. Pretreatment of the cells with the specific T-type Ca2+ channel blocker mibefradil occluded these inhibitory effects of ES. CONCLUSION AND IMPLICATIONS This study provides the first evidence that the antitumour effects of ES on glioblastoma cells is through direct inhibition of T-type Ca2+ channels and gives new insights into the future development of a new class of antiglioblastoma agents that target the proliferation and migration of these cells. LINKED ARTICLE This article is commented on by Santoni et al., pp. 12441246 of this issue. To view this commentary visit
基金：
This work was supported by National Natural Science Foundation
of China (No. 30900437 and 81171056), Natural
Science Funding of Jiangsu Province (No. BK2009118 and
BK2011440), Natural Science Funding for Colleges and Universities
in Jiangsu Province (No. 09KJB180008), Scientific
Research Foundation for the Returned Overseas Chinese
Scholars of State Education Ministry (JT), Start-up Funding of
Soochow University (No. Q4134901) and Dong-Wu Scholar
Funding of Soochow University (JT).
第一作者机构：[1]The Special Procurement Ward & Department of Neurology, the Second Affiliated Hospital of Soochow University, Suzhou, China,[2]Institute of Neuroscience, Soochow University, Suzhou, China,
通讯作者：
通讯机构：[*]Department of Neurobiology and Medical Psychology, Medical College of Soochow University, 199 Ren-Ai Road, Suzhou 215123, China.
推荐引用方式(GB/T 7714)：
Yuan Zhang,Junhong Zhang,Dongsheng Jiang,et al.Inhibition of T-type Ca2+channels by endostatin attenuates human glioblastoma cell proliferation and migration[J].BRITISH JOURNAL OF PHARMACOLOGY.2012,166(4):1247-60.doi:10.1111/j.1476-5381.2012.01852.x.
APA：
Yuan Zhang,Junhong Zhang,Dongsheng Jiang,Dong Zhang,Zhiyuan Qian...&Jin Tao.(2012).Inhibition of T-type Ca2+channels by endostatin attenuates human glioblastoma cell proliferation and migration.BRITISH JOURNAL OF PHARMACOLOGY,166,(4)
MLA：
Yuan Zhang,et al."Inhibition of T-type Ca2+channels by endostatin attenuates human glioblastoma cell proliferation and migration".BRITISH JOURNAL OF PHARMACOLOGY 166..4(2012):1247-60
医学