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浙江大学学报(医学版)  2015, Vol. 44 Issue (6): 678-683    DOI: 10.3785/j.issn.1008-9292.2015.11.13
综述     
纳秒脉冲电场肿瘤电消融的分子生物学机制
岑超, 陈新华, 郑树森
浙江大学附属第一医院肝胆胰外科, 浙江 杭州 310003
Mechanism of ablation with nanosecond pulsed electric field
CEN Chao, CHEN Xin-hua, ZHENG Shu-sen
Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
全文: PDF(594 KB)  
摘要: 

近年来,纳秒脉冲技术的临床应用研究不断深入与发展,但是其治疗的细胞学机制至今仍未完全阐明。在学术界存在各种假说和理论。研究证实,纳秒脉冲电场可以穿透细胞膜形成纳米孔,引起钙离子内流;也可作用于细胞内膜,引起内质网损伤、线粒体膜电位差的改变;进一步还可以损伤细胞微丝骨架,导致细胞形态的变化。本文结合最新的研究进展,围绕纳秒脉冲电场对细胞膜和细胞器的分子作用机制进行介绍。

关键词 肿瘤/治疗电穿孔辐射, 电离激光细胞/辐射效应综述    
Abstract

Nanosecond pulsed electric field ablation has been widely applied in clinical cancer treatment, while its molecular mechanism is still unclear. Researchers have revealed that nanosecond pulsed electric field generates nanopores in plasma membrane, leading to a rapid influx of Ca2+; it has specific effect on intracellular organelle membranes, resulting in endoplasmic reticulum injuries and mitochondrial membrane potential changes. In addition, it may also change cellular morphology through damage of cytoskeleton. This article reviews the recent research advances on the molecular mechanism of cell membrane and organelle changes induced by nanosecond pulsed electric field ablation.

Key wordsNeoplasms/therapy    Electroporation    Radiation, ionizing    Lasers    Cells/radiation effects    Review
收稿日期: 2015-06-30 出版日期: 2015-11-12
CLC:  R730.5  
基金资助:

国家自然科学基金(81372425);浙江省自然科学基金(LY13H180003);新疆维吾尔自治区重点实验室专项资金(2014KL002)

通讯作者: 郑树森(1950-),男,博士,教授,主任医师,博士生导师,主要从事肝胆外科工作和肝移植临床研究;E-mail:zyzss@zju.edu.cn;http://orcid.org/0000-0002-9745-5065     E-mail: zyzss@zju.edu.cn
作者简介: 岑超(1989-),男,博士研究生,主要从事纳秒脉冲电场肿瘤电消融的作用机制研究;E-mail:cenchao07@163.com;http://orcid.org/0000-0002-9738-7242
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引用本文:

岑超等. 纳秒脉冲电场肿瘤电消融的分子生物学机制[J]. 浙江大学学报(医学版), 2015, 44(6): 678-683.
CEN Chao, CHEN Xin-hua, ZHENG Shu-sen. Mechanism of ablation with nanosecond pulsed electric field. Journal of ZheJiang University(Medical Science), 2015, 44(6): 678-683.

链接本文:

http://www.zjujournals.com/xueshu/med/CN/10.3785/j.issn.1008-9292.2015.11.13      或      http://www.zjujournals.com/xueshu/med/CN/Y2015/V44/I6/678

[1] NEUMANN E, SCHAEFER-RIDDER M, WANG Y, et al. Gene transfer into mouse lyoma cells by electroporation in high electric fields[J]. EMBO J, 1982, 1(7):841-845.
[2] ZIMMERMANN U, FRIEDRICH U, MUSSAUER H, et al. Electromanipulation of mammalian cells: fundamentals and application[J]. Ieee T Plasma Sci, 2000, 28(1):72-82.
[3] NEUMANN E, KAKORIN S, TOENSING K. Fundamentals of electroporative delivery of drugs and genes[J]. Bioelectrochem Bioenerg, 1999, 48(1):3-16.
[4] WEAVER J C, VAUGHAN T E, CHIZMADZHEV Y. Theory of electrical creation of aqueous pathways across skin transport barriers[J]. Adv Drug Deliv Rev, 1999, 35(1):21-39.
[5] BELEHRADEK M, DOMENGE C, LUBOINSKI B, et al. Electrochemotherapy, a new antitumor treatment.first clinical phase i-ii trial[J]. Cancer, 1993, 72(12):3694-3700.
[6] DEV S B, RABUSSAY D P, WIDERA G, et al. Medical applications of electroporation[J]. Ieee T Plasma Sci, 2000, 28(1):206-223.
[7] HELLER R, JAROSZESKI M J, GLASS L F, et al. Phase I/II trial for the treatment of cutaneous and subcutaneous tumors using electrochemotherapy[J]. Cancer, 1996, 77(5):964-971.
[8] HOFMANN F, OHNIMUS H, SCHELLER C, et al. Electric field pulses can induce apoptosis[J]. J Membr Biol, 1999, 169(2):103-109.
[9] SCHOENBACH K H, BEEBE S J, BUESCHER E S. Intracellular effect of ultrashort electrical pulses[J]. Bioelectromagnetics, 2001, 22(6):440-448.
[10] BEEBE S J, FOX P M, REC L J, et al. Nanosecond pulsed electric field (nsPEF) effects on cells and tissues: apoptosis induction and tumor growth inhibition[J]. Ieee T Plasma Sci, 2002, 30(1):286-292.
[11] HAIR P S, SCHOENBACH K H, BUESCHER E S. Sub-microsecond, intense pulsed electric field applications to cells show specificity of effects[J]. Bioelectrochemistry, 2003, 61(1-2):65-72.
[12] STACEY M, STICKLEY J, FOX P, et al. Differential effects in cells exposed to ultra-short, high intensity electric fields: cell survival, DNA damage, and cell cycle analysis[J]. Mutat Res, 2003, 542(1-2):65-75.
[13] VERNIER P T, SUN Y, MARCU L, et al. Calcium bursts induced by nanosecond electric pulses[J]. Biochem Biophys Res Commun, 2003, 310(2):286-295.
[14] DENG J, SCHOENBACH K H, BUESCHER E S, et al. The effects of intense submicrosecond electrical pulses on cells[J]. Biophys J, 2003, 84(4):2709-2714.
[15] ONIK G, MIKUS P, RUBINSKY B. Irreversible electroporation: implications for prostate ablation[J]. Technol Cancer Res Treat, 2007, 6(4):295-300.
[16] IVORRA A, RUBINSKY B. Historical review of irreversible electroporation in medicine[J]. Series in Biomedical Engineering, 2010, 1-21.
[17] RUBINSKY B, ONIK G, MIKUS P. Irreversible electroporation: a new ablation modality-clinical implications[J]. Technol Cancer Res Treat, 2007, 6(1):37-48.
[18] NUCCITELLI R, WOOD R, KREIS M, et al. First-in-human trial of nanoelectroablation therapy for basal cell carcinoma: proof of method[J]. Exp Dermatol, 2014, 23(2):135-137.
[19] BOWMAN A M, NESIN O M, PAKHOMOVA O N, et al. Analysis of plasma membrane integrity by fluorescent detection of Tl(+) uptake[J]. J Membr Biol, 2010, 236(1):15-26.
[20] NESIN O M, PAKHOMOVA O N, XIAO S, et al. Manipulation of cell volume and membrane pore comparison following single cell permeabilization with 60-and 600-ns electric pulses[J]. Biochim Biophys Acta, 2011, 1808(3):792-801.
[21] PAKHOMOV A G, KOLB J F, WHITE J A, et al. Long-lasting plasma membrane permeabilization in mammalian cells by nanosecond pulsed electric field (nspef)[J]. Bioelectromagnetics, 2007, 28(8):655-663.
[22] BEEBE S J, SAIN N M, REN W. Induction of cell death mechanisms and apoptosis by nanosecond pulsed electric fields (nsPEFs)[J]. Cells, 2013, 2(1):136-162.
[23] SUGAR I P, NEUMANN E. Stochastic model for electric field-induced membrane pores. electroporation[J]. Biophys Chem, 1984, 19(3):211-225.
[24] WEAVER J C. Electroporation of biological membranes from multicellular to nano scales[J]. Ieee T Dielect El In, 2003, 10(5):754-768.
[25] CRAVISO G L, CHOE S, CHATTERJEE P, et al. Nanosecond electric pulses: a novel stimulus for triggering Ca2+ influx into chromaffin cells via voltage-gated Ca2+ channels[J]. Cell Mol Neurobiol, 2010, 30(8):1259-1265.
[26] DRESSLER V, SCHWISTER K, HAEST C W, et al. Dielectric breakdown of the erythrocyte membrane enhances transbilayer mobility of phospholipids[J]. Biochim Biophys Acta, 1983, 732(1):304-307.
[27] HAEST C W, KAMP D, DEUTICKE B. Transbilayer reorientation of phospholipid probes in the human erythrocyte membrane. lessons from studies on electroporated and resealed cells[J]. Biochim Biophys Acta, 1997, 1325(1):17-33.
[28] VERNIER P T, SUN Y, MARCU L, et al. Nanoelectropulse-induced phosphatidylserine translocation[J]. Biophys J, 2004, 86(6):4040-4048.
[29] VERHOVEN B, SCHLEGEL R A, WILLIAMSON P. Mechanisms of phosphatidylserine exposure, a phagocyte recognition signal, on apoptotic t lymphocytes[J]. J Exp Med, 1995, 182(5):1597-1601.
[30] VINCELETTE R L, ROTH C C, MCCONNELL M P, et al. Thresholds for phosphatidylserine externalization in chinese hamster ovarian cells following exposure to nanosecond pulsed electrical fields (nsPEF)[J]. PLoS One, 2013, 8(4):e63122.
[31] PAKHOMOVA O N, KHOROKHORINA V A, BOWMAN A M, et al. Oxidative effects of nanosecond pulsed electric field exposure in cells and cell-free media[J]. Arch Biochem Biophys, 2012, 527(1):55-64.
[32] HIGUCHI Y. Glutathione depletion-induced chromosomal DNA fragmentation associated with apoptosis and necrosis[J]. J Cell Mol Med, 2004, 8(4):455-464.
[33] WEYEMI U, DUPUY C. The emerging role of ros-generating nadph oxidase nox4 in DNA-damage responses[J]. Mutat Res, 2012, 751(2):77-81.
[34] GARCIA-PEREZ C, ROY S S, NAGHDI S, et al. Bid-induced mitochondrial membrane permeabilization waves propagated by local reactive oxygen species (ROS) signaling[J]. Proc Natl Acad Sci U S A, 2012, 109(12):4497-4502.
[35] BONNAFOUS P, VERNHES M C, TEISSIE J, et al. The generation of reactive-oxygen species associated with long-lasting pulse-induced electropermeabilisation of mammalian cells is based on a non-destructive alteration of the plasma membrane[J]. Biochim Biophys Acta, 1999, 1461(1):123-134.
[36] NUCCITELLI R, LUI K, KREIS M, et al. nanosecond pulsed electric field stimulation of reactive oxygen species in human pancreatic cancer cells is Ca(2+)-dependent[J]. Biochem Biophys Res Commun, 2013, 435(4):580-585.
[37] SEMENOV I, XIAO S, PAKHOMOV A G. Primary pathways of intracellular Ca(2+) mobilization by nanosecond pulsed electric field[J]. Biochim Biophys Acta, 2013, 1828(3):981-989.
[38] WHITE J A, BLACKMORE P F, SCHOENBACH K H, et al. Stimulation of capacitative calcium entry in HL-60 cells by nanosecond pulsed electric fields[J]. J Biol Chem, 2004, 279(22):22964-22972.
[39] VERNIER P T, SUN Y, CHEN M T, et al. Nanosecond electric pulse-induced calcium entry into chromaffin cells[J]. Bioelectrochemistry, 2008, 73(1):1-4.
[40] CRAVISO G L, CHOE S, CHATTERJEE I, et al. Modulation of intracellular Ca2+ levels in chromaffin cells by nanoelectropulses[J]. Bioelectrochemistry, 2012, 87:244-252.
[41] PAKHOMOV A G, SEMENOV I, XIAO S, et al. Cancellation of cellular responses to nanoelectroporation by reversing the stimulus polarity[J]. Cell Mol Life Sci, 2014, 71(22):4431-4441.
[42] REDDY A, CALER E V, ANDREWS N W. Plasma membrane repair is mediated by Ca(2+)-regulated exocytosis of lysosomes[J]. Cell, 2001, 106(2):157-169.
[43] CZIBENER C, SHERER N M, BECKER S M, et al. Ca2+ and synaptotagmin Ⅶ-dependent delivery of lysosomal membrane to nascent phagosomes[J]. J Cell Biol, 2006, 174(7):997-1007.
[44] BEEBE S J, FOX P M, REC L J, et al. Nanosecond, high-intensity pulsed electric fields induce apoptosis in human cells[J]. FASEB J, 2003, 17(11):1493-1495.
[45] ESTLACK L E, ROTH C C, THOMPSON G L, et al. Nanosecond pulsed electric fields modulate the expression of Fas/CD95 death receptor pathway regulators in U937 and Jurkat cells[J]. Apoptosis, 2014, 19(12):1755-1768.
[46] IBEY B L, PAKHOMOV A G, GREGORY B W, et al. Selective cytotoxicity of intense nanosecond-duration electric pulses in mammalian cells[J]. Biochim Biophysica Acta, 2010, 1800(11):1210-1219.
[47] IBEY B L, ROTH C C, PAKHOMOV A G, et al. Dose-dependent thresholds of 10-ns electric pulse induced plasma membrane disruption and cytotoxicity in multiple cell lines[J]. PLoS One, 2011, 6(1):e15642.
[48] ANDRE F M, RASSOKHIN M A, BOWMAN A M, et al. Gadolinium blocks membrane permeabilization induced by nanosecond electric pulses and reduces cell death[J]. Bioelectrochemistry, 2010, 79(1):95-100.
[49] PAKHOMOV A G, SHEVIN R, WHITE J A, et al. Membrane permeabilization and cell damage by ultrashort electric field shocks[J]. Arch Biochem Biophys, 2007, 465(1):109-118.
[50] IBEY B L, PAKHOMOV A G, GREGORY B W, et al. Selective cytotoxicity of intense nanosecond-duration electric pulses in mammalian cells[J]. Biochim Biophys Acta, 2010, 1800(11):1210-1219.
[51] ULLERY J C, TARANGO M, ROTH C C, et al. Activation of autophagy in response to nanosecond pulsed electric field exposure[J]. Biochem Biophys Res Commun, 2015, 458(2):411-417.
[52] THOMPSON G L, ROTH C C, DALZELL D R, et al. Calcium influx affects intracellular transport and membrane repair following nanosecond pulsed electric field exposure[J]. J Biomed Opt, 2014, 19(5):055005.
[53] DUTTA D, ASMAR A, STACEY M. Effects of nanosecond pulse electric fields on cellular elasticity[J]. Micron, 2015, 72:15-20.
[54] STACEY M, STICKLEY J, FOX P, et al. Differential effects in cells exposed to ultra-short, high intensity electric fields: cell survival, DNA damage, and cell cycle analysis[J]. Mutat Res, 2003, 542(1-2):65-75.
[55] STACEY M, FOX P, BUESCHER S, et al. Nanosecond pulsed electric field induced cytoskeleton, nuclear membrane and telomere damage adversely impact cell survival[J]. Bioelectrochemistry, 2011, 82(2):131-134.
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