As_2O_3诱导肿瘤细胞凋亡依赖H_2O_2途径

细胞凋亡

中国病理生理杂志 ChineseJournalofPathophysiology 2006,22(6):1185-

As_2O_3诱导肿瘤细胞凋亡依赖H_2O_2途径

1190

[文章编号] 1000-4718(2006)06-1185-06

1185

As2O3诱导肿瘤细胞凋亡依赖H2O2途径3

曹 娟#, 郑 杰△

(东南大学基础医学院,病理与病理生理学系,分子病理研究所,江苏南京210009)

  [摘 要] 目的:探讨三氧化二砷(arsenictrioxide,As2O3)对人乳头瘤病毒(HPV)阳性宫颈癌HeLa细胞和HPV阴性胰腺癌AsPC-1细胞的凋亡诱导作用与细胞内H2O2水平的关系。方法:采用不同浓度的As2O3处理HeLa细胞和AsPC-1细胞不同时段,显微镜下观察细胞的凋亡,噻唑蓝(MTT)法测定细胞生长抑制情况;不同浓度的As2O3处理细胞2、5、8、12、24h后,用DCFH-DA标记检测细胞内的H2O2水平。结果:2μmol/LAs2O3处理HeLa细胞48h后细胞的生长受到明显抑制,表现出细胞凋亡的特征,随着As2O3浓度的增加和作用时间的延长效果更加明显。而1μmol/LAs2O3处理AsPC-1细胞24h即呈现明显的生长抑制和凋亡特征。As2O3处理细胞2h细胞内H2O2的水平比对照组升高(10μmol/L组达51130%),持续到8h达到高峰(升高84119%),12,24h水平与对照组接近,并有明显的剂量依赖性。As2O3处理AsPC-1细胞2h后,H2O2(10μmol/L组达

79%),持续到5h达到高峰(增高169%),且该细胞内H2O2h之后的变化情况与HeLa细胞类似。结论:As2O3诱导HeLa细胞和AsPC-12O2,而与HPV的感染

无明显相关性。H2O2积累是As2O32As2O3诱导肿瘤细胞凋亡途径中扮演类似第二信使的作用。

[关键词] ;;;HeLa细胞

  [中图分类号] [] A

Solidapoptosisinducedbyarsenictrioxideisrelatedtogenerationofreactiveoxygenspecies

CAOJuan,ZHENGJie

(MolecularPathologyInstitute,DepartmentofPathologyandPathophysiology,SchoolofBasicMedicalScience,SoutheastUniversi2ty,Nanjing210009,China)

  [ABSTRACT] AIM:TostudytheeffectsofAs2O3onthegrowthofhumancervicalcarcinomacellline,HeLacells,hu2manpancreaticcarcinomacellline,AsPC-1cells,andthegenerationofreactiveoxygenspecies(ROS)inthecells.METH2

ODS:HeLacellsandAsPC-1cellsweretreatedwithvariousconcentrationsofAs2O3.TheeffectsofAs2O3onHeLacellsandAs2PC-1cellssurvivalandapoptosisweredeterminedbyMTTassayandlightmicroscope,andcellularROSwasalsomeasuredbyflu2orometer.RESULTS:Afterbeingtreatedwith2μmol/LAs2O3for48h,thesurvivalofHeLacellswasdecreased,amarkedapop2tosischaracteristicwasobservedintime-anddose-dependentmanner.However,thesurvivalofAsPC-1cellsmarkedlyde2

μcreasedafterbeingtreatedwitheven1mol/LAs2O3for24h.Whenwemeasuredthecellularhydrogenperoxide(H2O2)level,we

foundthattheH2O2levelinHeLacellsstartedtoriseafterbeingincubatedwithAs2O3for2h,andsustainedincreased,reachedthepeakofH2O2levelat8h,thenitbegantodecrease.WhiletheH2O2levelinAsPC-1cellsstartedtoriseat2h,reachedthehighestpointat5h,afterwhichitbegantodescend.At12h,theH2O2levelinHeLacellsandAsPC-1cellsweresimilartothatofthecontrolgroup.CONCLUSION:ThemolecularmechanismsunderlyingAs2O3-inducedapoptosisincellsderivedfromthesolidtumorsmayberelatedtothecellularROSlevel.

  [KEYWORDS] As2O3;Neoplasms;Apoptosis;Reactiveoxygenspecies;HeLacells

  三氧化二砷(arsenictrioxide,As2O3)是一种具有抗肿瘤作用的药物[16],它在治疗急性早幼粒细胞白血病(acutepromyelocyticleukemia,APL)的疗效已得

 [收稿日期]2004-09-17   [修回日期]2004-12-20

到国内外肯定。近年来的研究表明As2O3对实体肿瘤也有一定的治疗作用[1]。宫颈癌和胰腺癌均为人类常见的恶性肿瘤,宫颈癌的发生与人乳头瘤病毒

3[基金项目]教育部留学回国人员科研启动基金资助项目(No.6823001004)△通信作者Tel:025-83272358;E-mail:jiezheng54@http://www.51wendang.com

#现工作单位:南京市鼓楼医院,江苏南京210008

Word文档免费下载Word文档免费下载:As_2O_3诱导肿瘤细胞凋亡依赖H_2O_2途径 (共6页,当前第1页)

As_2O_3诱导肿瘤细胞凋亡依赖H_2O_2途径相关文档

最新文档

返回顶部