[1]李卫玲,李超英,茹 琴.钾通道阻断剂对胶质瘤细胞迁移和侵袭的影响[J].江西师范大学学报(自然科学版),2017,(02):150-154.
 LI Weiling,LI Chaoying,RU Qin.Effect of Potassium Channel Blockers on Migration and Invasion of Human Glioma Cells[J].,2017,(02):150-154.
点击复制

钾通道阻断剂对胶质瘤细胞迁移和侵袭的影响()
分享到:

《江西师范大学学报》(自然科学版)[ISSN:1006-6977/CN:61-1281/TN]

卷:
期数:
2017年02期
页码:
150-154
栏目:
出版日期:
2017-03-01

文章信息/Info

Title:
Effect of Potassium Channel Blockers on Migration and Invasion of Human Glioma Cells
作者:
李卫玲李超英茹 琴
江汉大学武汉生物医学研究院,湖北 武汉 430056
Author(s):
LI WeilingLI ChaoyingRU Qin
Wuhan Insititutes of Biomedical Science,Jianghan University,Wuhan Hubei 430056,China
关键词:
钾通道 神经胶质瘤 迁移 侵袭 阻断剂
Keywords:
potassium channels glioma cell migration invasion blockers
分类号:
Q 25; R 739.4
文献标志码:
A
摘要:
为了检测电压门控钾通道阻断剂4-氨基吡啶(4-AP)、四乙胺(TEA)和ATP敏感钾通道阻断剂格列苯脲(Glibenclamide,Gli)对胶质瘤细胞迁移和侵袭的影响,选用人胶质瘤细胞系U87和U251,其中钾通道阻断剂4-AP、TEA及Gli处理作为实验组,未处理的作为对照组.采用划痕实验和Transwell小室法检测钾通道阻断剂对U87和U251细胞迁移和侵袭能力的影响; Western blot检测药物处理后细胞高迁移率蛋白B1(high mobility group protein B1,HMGB1)表达水平.结果表明:5 mmol·L-1的4-AP、40 mmol·L-1的TEA及400 μmol·L-1的Gli可以显著抑制胶质瘤细胞的迁移、侵袭,并降低HMGB1表达水平.电压门控钾通道和ATP敏感钾通道对胶质瘤细胞迁移和侵袭具有重要调控作用,3种钾通道阻断剂对胶质瘤细胞迁移和侵袭有不同程度的抑制作用,可能通过调控HMGB1相关通路实现.
Abstract:
To explore the effect of potassium channel blocker on glioma migration and invasion,voltage-gated potassium channel blocker 4-aminopyridine,tetraethylammonium and ATP sensitive potassium channel blocker glibenclamide were investigated.Human glioma cell lines U87 and U251 were selected to use.Wound-healing assay and Transwell assays were performed to determine the migration and invasion of glioma cells.The expression level of HMGB1 protein was detected by western blot.Cell abilities of migration and invasion were significantly reduced with 4-AP(5 mmol·L-1),TEA(40 mmol·L-1)or glibenclamide(400 μmol·L-1)compared with that of the control.The expression level of HMGB1 was significantly down-regulated in the blockers groups.Potassium channels play important roles in the migration and invasion of human glioma.The selective blockers of voltage-gated potassium channels or ATP-sensitive potassium channels significantly inhibited the migration and invasion of U87 and U251 cells,and down-regulation of HMGB1 gene expressions might be its possible mechanism.

参考文献/References:

[1] Holland E C.Gliomagenesis:genetic alterations and mouse models [J].Nat Rev Genet,2001,2:120-129.
[2] Maher E A,Furnari F B,Bachoo R M,et al.Malignant glioma:genetics and biology of a grave matter [J].Genes Dev,2001,15:1311-1333.
[3] Ru Qing,Shang Boyang,Miao Qinfang,et al.A cell penetrating peptide-integrated and enediyne-energized fusion protein shows potent antitumor activity [J].Eur J Pharm Sci,2012,47:781-789.
[4] Van Meir E G,Hadjipanayis C G,Norden A D,et al.Exciting new advances in neuro-oncology:the avenue to a cure for malignant glioma [J].CA Cancer J Clin,2010,60:166-193.
[5] Zhorov B S.Interactions of drugs and toxins with permeant ions in potassium,sodium,and calcium channels [J].Ross Fiziol Zh Im I M Sechenova,2011,97:661-677.
[6] Becchetti A.Ion channels and transporters in cancer [J].Am J Physiol Cell Physiol,2011,301:C255-C265.
[7] Stuhmer W,Alves F,Hartung F,et al.Potassium channels as tumour markers [J].FEBS Lett,2006,580:2850-2852.
[8] Asanuma M,Abdullaev I F,Rudkouskaya A,et al.Calcium-activated potassium channels BK and IK1 are functionally expressed in human gliomas but do not regulate cell proliferation [J].Plos One,2010,5:e12304.
[9] Huang Lianga,Li Boxing,Li Wenjun,et al.ATP-sensitive potassium channels control glioma cells proliferation by regulating ERK activity [J].Carcinogenesis,2009,30:737-744.
[10] Masi A,Becchetti A,Restano-Cassulini R,et al.hERG1 channels are overexpressed in glioblastoma multiforme and modulate VEGF secretion in glioblastoma cell lines [J].Br J Cancer,2005,93:781-792.
[11] Weaver A K,Bomben V C,Sontheimer H.Expression and function of calcium-activated potassium channels in human glioma cells [J].Glia,2006,54:223-233.
[12] Cherubini A,Hofmann G,Pillozzi S,et al.Human ether-a-go-go-related gene 1 channels are physically linked to beta1 integrins and modulate adhesion-dependent signaling [J].Mol Biol Cell,2005,16(6):2972-2983.
[13] Kraft R,Krause P,Jung S,et al.BK channel openers inhibit migration of human glioma cells [J].Pflugers Arch,2003,446(2):248-255.
[14] Catacuzzeno L,Aiello F,Fioretti B,et al.Serum-activated K and Cl currents underlay U87-MG glioblastoma cell migration [J].J Cell Physiol,2011,226(7):1926-1933.
[15] D’Alessandro G,Catalano M,Sciaccaluga M,et al.KCa3.1 channels are involved in the infiltrative behavior of glioblastoma in vivo [J].Cell Death Dis,2013,4:e773.
[16] Veeravalli K K,Ponnala S,Chetty C,et al.Integrin α9β1-mediated cell migration in glioblastoma via SSAT and Kir4.2 potassium channel pathway [J].Cell Signal,2012,24(1):272-281.
[17] Ru Qin,Tian Xiang,Wu Yuxiang,et al.Voltage-gated and ATP-sensitive K+ channels are associated with cell proliferation and tumorigenesis of human glioma [J].Oncol Rep,2014,31(2):842-848.
[18] Lastraioli E,Guasti L,Crociani O,et al.herg1 gene and HERG1 protein are overexpressed in colorectal cancers and regulate cell invasion of tumor cells [J].Cancer Research,2004,64(2):606-611.
[19] Zhou Qing,Kwan H Y,Chan H C,et al.Blockage of voltage-gated K+ channels inhibits adhesion and proliferation of hepatocarcinoma cells [J].Int J Mol Med,2003,11(2):261-266.
[20] Kostova N,Zlateva S,Ugrinova I,et al.The expression of HMGB1 protein and its receptor RAGE in human malignant tumors [J].Mol Cell Biochem,2010,337(1/2):251-258.
[21] Rauvala H,Rouhiainen A.Physiological and pathophysiological outcomes of the interactions of HMGB1 with cell surface receptor [J].Biochim Biophys Acta,2010,1799(1/2):164-170.

备注/Memo

备注/Memo:
收稿日期:2016-11-20基金项目:国家自然科学基金青年科学基金(81302203)资助项目.通信作者:茹 琴(1984-),女,河南三门峡人,副研究员,博士,主要从事恶性肿瘤发病机制及小分子靶向扶肿瘤药物的研发.E-mail:ruq.whibs@aliyun.com
更新日期/Last Update: 1900-01-01