摘要
活性氧(ROS)是诱导生物体内氧化应激的重要分子,在肿瘤发生,肿瘤进展和复发中起关键作用。 ROS的最新发现表明,ROS可以加速肿瘤细胞的死亡,因此可以用于治疗癌症。目前,旨在增加肿瘤细胞的ROS水平的促氧化剂药物已经在临床中广泛使用。但是,ROS在治疗肿瘤方面是一把双刃剑。高水平的ROS不仅会导致肿瘤细胞死亡,还会导致正常细胞(尤其是骨髓造血细胞)的氧化损伤,从而导致骨髓抑制和(或)其他副作用,肿瘤治疗效果差,甚至威胁患者的生命。生活。如何增强ROS对肿瘤细胞的杀伤作用,同时又避免了对正常细胞的氧化损伤,已成为当务之急。这项研究是对ROS介导的程序性死亡在肿瘤治疗以及预防和治疗ROS诱导的骨髓氧化损伤的作用中的最新进展的综述。
关键词: ROS,程序性细胞死亡,骨髓保护,化学疗法,肿瘤,造血作用。
图形摘要
[http://dx.doi.org/10.4110/in.2018.18.e14] [PMID: 29503744]
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.11.014] [PMID: 30448512]
[http://dx.doi.org/10.1016/j.freeradbiomed.2017.05.024] [PMID: 28578013]
[http://dx.doi.org/10.1007/s13346-018-0579-4] [PMID: 30136122]
[http://dx.doi.org/10.1021/acs.jmedchem.6b01243] [PMID: 28135088]
[http://dx.doi.org/10.1586/17474086.2015.1049593] [PMID: 26149913]
[http://dx.doi.org/10.1038/emm.2016.119] [PMID: 27811934]
[http://dx.doi.org/10.3390/ijms18112265] [PMID: 29143796]
[http://dx.doi.org/10.4103/jpp.JPP_93_16] [PMID: 28405135]
[PMID: 26270131]
[http://dx.doi.org/10.1158/1078-0432.CCR-06-2082] [PMID: 17289868]
[http://dx.doi.org/10.21873/anticanres.11182] [PMID: 27793920]
[http://dx.doi.org/10.1016/j.critrevonc.2017.02.004] [PMID: 28325262]
[http://dx.doi.org/10.1038/nature07733] [PMID: 19194462]
[http://dx.doi.org/10.1002/jcp.22764] [PMID: 21448925]
[http://dx.doi.org/10.1038/nrd2803] [PMID: 19478820]
[http://dx.doi.org/10.1038/nature10189] [PMID: 21734707]
[http://dx.doi.org/10.1016/j.ccr.2014.08.002]
[http://dx.doi.org/10.1016/j.freeradbiomed.2009.12.022] [PMID: 20045723]
[http://dx.doi.org/10.1016/S0014-5793(98)00228-2] [PMID: 9559649]
[http://dx.doi.org/10.1016/j.jss.2007.03.048] [PMID: 17574045]
[http://dx.doi.org/10.1016/S0304-3835(02)00074-5] [PMID: 12175526]
[http://dx.doi.org/10.1007/s11010-014-1979-5] [PMID: 24488173]
[http://dx.doi.org/10.1016/j.bbrc.2009.12.144] [PMID: 20043871]
[http://dx.doi.org/10.1016/j.expneurol.2017.10.031] [PMID: 29104115]
[http://dx.doi.org/10.1016/j.cbi.2011.01.010] [PMID: 21241685]
[http://dx.doi.org/10.1074/jbc.M409663200] [PMID: 15485871]
[http://dx.doi.org/10.1007/978-94-017-9211-0_18] [PMID: 25201203]
[http://dx.doi.org/10.1038/cdd.2010.19] [PMID: 20203691]
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.02.031] [PMID: 21382479]
[http://dx.doi.org/10.1101/gad.1376506] [PMID: 16391229]
[http://dx.doi.org/10.1186/1471-2407-13-580] [PMID: 24314238]
[http://dx.doi.org/10.1016/j.cell.2009.05.037] [PMID: 19524513]
[http://dx.doi.org/10.1007/s10495-017-1375-1] [PMID: 28424988]
[http://dx.doi.org/10.1172/JCI39987] [PMID: 20200450]
[http://dx.doi.org/10.1158/1535-7163.MCT-06-0511] [PMID: 17513612]
[http://dx.doi.org/10.1038/onc.2016.310] [PMID: 27869161]
[http://dx.doi.org/10.1007/s13277-015-4258-5] [PMID: 26496737]
[http://dx.doi.org/10.1038/cddis.2013.320] [PMID: 24030154]
[http://dx.doi.org/10.1038/s41580-018-0003-4] [PMID: 29618831]
[http://dx.doi.org/10.1007/s00432-017-2557-5] [PMID: 29288363]
[http://dx.doi.org/10.1016/j.cmet.2017.04.004] [PMID: 28467923]
[http://dx.doi.org/10.4155/fmc.15.88] [PMID: 26334206]
[http://dx.doi.org/10.1038/onc.2014.25] [PMID: 24662833]
[http://dx.doi.org/10.1042/BCJ20160177] [PMID: 27208176]
[http://dx.doi.org/10.18632/oncotarget.12313] [PMID: 27689330]
[http://dx.doi.org/10.18632/oncotarget.19409] [PMID: 29207624]
[http://dx.doi.org/10.1038/cddis.2011.36] [PMID: 21525939]
[http://dx.doi.org/10.3892/ijo.2015.2937] [PMID: 25825088]
[http://dx.doi.org/10.1371/journal.pone.0135236] [PMID: 26288183]
[http://dx.doi.org/10.1016/j.yexcr.2015.04.010] [PMID: 25912909]
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.10.487] [PMID: 22094224]
[http://dx.doi.org/10.1038/cddis.2013.17] [PMID: 23392177]
[http://dx.doi.org/10.3892/ijmm.2018.3499] [PMID: 29484365]
[http://dx.doi.org/10.18632/oncotarget.10836] [PMID: 27474168]
[http://dx.doi.org/10.1002/jcb.24808] [PMID: 24619908]
[http://dx.doi.org/10.1371/journal.pone.0173712] [PMID: 28301876]
[http://dx.doi.org/10.1111/j.1582-4934.2009.00663.x] [PMID: 20196784]
[http://dx.doi.org/10.1159/000452532] [PMID: 27855364]
[http://dx.doi.org/10.1016/j.canlet.2015.01.039] [PMID: 25644089]
[http://dx.doi.org/10.1016/j.bmc.2007.10.033] [PMID: 17980607]
[http://dx.doi.org/10.1242/jcs.011163] [PMID: 18032788]
[http://dx.doi.org/10.1111/cas.12253] [PMID: 23952056]
[http://dx.doi.org/10.1073/pnas.0511288103] [PMID: 16547133]
[http://dx.doi.org/10.1016/j.bbrc.2011.07.036] [PMID: 21806968]
[http://dx.doi.org/10.1038/nature02041] [PMID: 14574412]
[http://dx.doi.org/10.1182/blood-2007-05-087759] [PMID: 17595331]
[http://dx.doi.org/10.1089/ars.2014.5941] [PMID: 24762207]
[http://dx.doi.org/10.1038/nature02989] [PMID: 15496926]
[http://dx.doi.org/10.2174/138945011796150325] [PMID: 21443463]
[http://dx.doi.org/10.1016/j.cell.2007.01.003] [PMID: 17254970]
[http://dx.doi.org/10.1084/jem.20081297] [PMID: 18809716]
[http://dx.doi.org/10.1182/blood-2009-09-241000] [PMID: 20354168]
[http://dx.doi.org/10.1038/nature08040] [PMID: 19404261]
[http://dx.doi.org/10.1097/MOH.0b013e328338c439] [PMID: 20308890]
[http://dx.doi.org/10.1016/j.stem.2010.09.013] [PMID: 21040902]
[http://dx.doi.org/10.1073/pnas.1120358109] [PMID: 22611193]
[http://dx.doi.org/10.1182/blood-2018-02-831669] [PMID: 29959189]
[http://dx.doi.org/10.1038/emm.2017.124] [PMID: 28857086]
[http://dx.doi.org/10.1038/srep37827] [PMID: 27886253]
[http://dx.doi.org/10.18632/oncotarget.1854] [PMID: 24797310]
[http://dx.doi.org/10.1158/1535-7163.MCT-16-0332] [PMID: 27550943]
[http://dx.doi.org/10.2174/138945012802009044] [PMID: 22594470]
[http://dx.doi.org/10.1016/j.fct.2010.03.027]
[http://dx.doi.org/10.1111/j.1742-7843.2010.00621.x] [PMID: 20722640]
[http://dx.doi.org/10.1016/j.redox.2017.08.003] [PMID: 28826042]
[http://dx.doi.org/10.1016/j.freeradbiomed.2012.02.007] [PMID: 22343421]
[http://dx.doi.org/10.3109/10715762.2011.591391] [PMID: 21682664]
[http://dx.doi.org/10.1089/ars.2008.2114] [PMID: 18627347]
[http://dx.doi.org/10.3390/ijms16022366] [PMID: 25622253]
[http://dx.doi.org/10.1016/j.ijrobp.2015.12.374] [PMID: 27026312]
[http://dx.doi.org/10.4103/2319-4170.125655] [PMID: 24667671]
[http://dx.doi.org/10.1016/j.stem.2007.03.002] [PMID: 18371340]
[http://dx.doi.org/10.1038/ncomms5901] [PMID: 25249323]
[http://dx.doi.org/10.1146/annurev.biochem.73.011303.073723] [PMID: 15189136]
[http://dx.doi.org/10.1007/s12185-011-0872-1] [PMID: 21567162]
[http://dx.doi.org/10.1016/j.mad.2004.09.034] [PMID: 15610769]
[http://dx.doi.org/10.1038/nm1388] [PMID: 16565722]
[PMID: 8968104]
[http://dx.doi.org/10.1016/j.canlet.2003.09.012] [PMID: 14670612]
[http://dx.doi.org/10.1021/cr500226n] [PMID: 25180889]
[http://dx.doi.org/10.2174/1389450115666141024113925] [PMID: 25341421]
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.04.016] [PMID: 21565268]
[http://dx.doi.org/10.7785/tcrt.2012.500260] [PMID: 22475066]
[http://dx.doi.org/10.1016/j.biopha.2009.09.009] [PMID: 19896793]
[http://dx.doi.org/10.1177/1010428317705759] [PMID: 28466788]
[http://dx.doi.org/10.1093/mutage/gev011] [PMID: 25778689]
[PMID: 10348264]
[http://dx.doi.org/10.1016/j.fct.2015.04.018] [PMID: 25910835]
[PMID: 10348259]
[http://dx.doi.org/10.3892/mmr.2017.6272] [PMID: 28260045]
[http://dx.doi.org/10.1002/ptr.3284] [PMID: 20740475]
[http://dx.doi.org/10.2174/138945012804545560] [PMID: 23140285]
[http://dx.doi.org/10.1016/j.ajog.2005.11.030] [PMID: 16647892]
[http://dx.doi.org/10.1111/j.1349-7006.2009.01297.x] [PMID: 19703194]
[http://dx.doi.org/10.1196/annals.1397.039] [PMID: 17404048]
[PMID: 15700780]
[http://dx.doi.org/10.1124/jpet.103.054676] [PMID: 12954803]
[http://dx.doi.org/10.1016/j.ejps.2013.08.005] [PMID: 23954456]
[http://dx.doi.org/10.1016/j.fct.2010.09.010] [PMID: 20837083]
[http://dx.doi.org/10.1074/jbc.M610616200] [PMID: 17360708]
[http://dx.doi.org/10.1155/2017/6160785] [PMID: 29147656]
[http://dx.doi.org/10.1016/j.ijbiomac.2015.12.046] [PMID: 26712703]
[http://dx.doi.org/10.1016/j.ijbiomac.2014.06.036] [PMID: 24984021]
[http://dx.doi.org/10.3390/ijms19020506] [PMID: 29419740]
[http://dx.doi.org/10.1016/j.ijbiomac.2017.12.081] [PMID: 29248551]
[http://dx.doi.org/10.1016/j.fct.2010.10.028] [PMID: 21056614]
[http://dx.doi.org/10.1016/j.carbpol.2011.07.068]
[http://dx.doi.org/10.1016/j.carbpol.2012.05.039] [PMID: 24751044]
[http://dx.doi.org/10.1155/2012/506214] [PMID: 23125868]
[http://dx.doi.org/10.1155/2013/827230] [PMID: 23533525]
[http://dx.doi.org/10.2147/DDDT.S115135] [PMID: 28096658]
[http://dx.doi.org/10.1093/ndt/gfr195] [PMID: 21602180]
[http://dx.doi.org/10.1016/j.fct.2013.07.022] [PMID: 23872129]
[http://dx.doi.org/10.1038/bjc.1996.673] [PMID: 8980410]
[http://dx.doi.org/10.1021/jf800175a] [PMID: 18522405]
[http://dx.doi.org/10.1093/carcin/bgy076] [PMID: 29860383]
[http://dx.doi.org/10.1631/jzus.B1600022] [PMID: 28124838]
[http://dx.doi.org/10.3892/mmr.2015.3266] [PMID: 25634350]
[http://dx.doi.org/10.1371/journal.pone.0109630]
[http://dx.doi.org/10.1186/s13045-014-0075-3] [PMID: 25270015]
[http://dx.doi.org/10.3892/mmr.2012.1023] [PMID: 22895548]
[http://dx.doi.org/10.1016/j.ijbiomac.2018.03.062] [PMID: 29653168]
[http://dx.doi.org/10.1021/jf4053012] [PMID: 24506418]
[http://dx.doi.org/10.18632/oncotarget.13481] [PMID: 27888812]
[http://dx.doi.org/10.1016/j.ijbiomac.2017.02.071] [PMID: 28235606]
[http://dx.doi.org/10.1038/srep26722] [PMID: 27216943]
[http://dx.doi.org/10.1016/j.carbpol.2015.11.051] [PMID: 26794745]
[http://dx.doi.org/10.1016/j.carbpol.2013.03.009] [PMID: 23648042]
[http://dx.doi.org/10.1016/j.taap.2018.05.025] [PMID: 29847772]
[http://dx.doi.org/10.1016/j.phymed.2018.03.035] [PMID: 29747757]
[http://dx.doi.org/10.1159/000488433] [PMID: 29590661]
[PMID: 29389802]
[http://dx.doi.org/10.3892/mmr.2013.1273] [PMID: 23314115]
[http://dx.doi.org/10.1155/2012/981675] [PMID: 22719792]
[http://dx.doi.org/10.1016/j.bcp.2017.12.004] [PMID: 29225132]
[http://dx.doi.org/10.1016/j.biopha.2017.10.147] [PMID: 29107932]
[PMID: 28679317]
[http://dx.doi.org/10.1016/j.biopha.2017.03.050] [PMID: 28391166]
[http://dx.doi.org/10.1038/aps.2016.34] [PMID: 27292614]
[http://dx.doi.org/10.1007/s13402-016-0273-9] [PMID: 27016209]
[http://dx.doi.org/10.3748/wjg.v24.i17.1901] [PMID: 29740205]
[http://dx.doi.org/10.1080/01635581.2016.1142587] [PMID: 26943028]
[http://dx.doi.org/10.1007/s10495-013-0820-z] [PMID: 23417763]
[http://dx.doi.org/10.3747/co.19.1139] [PMID: 22876162]
[http://dx.doi.org/10.1254/jphs.12193FP] [PMID: 23782641]
[http://dx.doi.org/10.1016/j.toxlet.2014.03.015] [PMID: 24680927]
[http://dx.doi.org/10.1186/s12906-016-1036-x] [PMID: 26861252]
[http://dx.doi.org/10.2147/OTT.S157707] [PMID: 29780252]
[http://dx.doi.org/10.1016/j.prp.2018.03.015] [PMID: 29567333]
[http://dx.doi.org/10.1155/2017/7126872] [PMID: 29362667]
[PMID: 29138869]
[http://dx.doi.org/10.1002/jcb.26006] [PMID: 28328092]
[http://dx.doi.org/10.1371/journal.pone.0165372] [PMID: 27792748]
[http://dx.doi.org/10.3390/molecules21101353] [PMID: 27754332]
[http://dx.doi.org/10.1016/j.phymed.2016.03.003] [PMID: 27161405]
[http://dx.doi.org/10.3892/or.2015.4054] [PMID: 26081590]
[http://dx.doi.org/10.1038/srep09987] [PMID: 25984950]
[http://dx.doi.org/10.1590/1414-431x20144293] [PMID: 25517919]
[http://dx.doi.org/10.1016/j.etap.2014.10.012] [PMID: 25461556]
[http://dx.doi.org/10.1007/s10495-013-0907-6] [PMID: 24052409]
[http://dx.doi.org/10.1016/j.phymed.2017.12.001] [PMID: 29433670]
[http://dx.doi.org/10.1007/s12032-015-0516-z] [PMID: 25737432]
[http://dx.doi.org/10.1016/j.bbrc.2018.02.009] [PMID: 29408335]
[http://dx.doi.org/10.1016/j.bbrc.2017.10.042] [PMID: 29024631]
[http://dx.doi.org/10.3892/mmr.2017.7633] [PMID: 28983599]
[http://dx.doi.org/10.1007/s00280-017-3299-4] [PMID: 28393257]
[http://dx.doi.org/10.3892/ijo.2015.2967] [PMID: 25892545]
[http://dx.doi.org/10.3109/10715762.2014.897342] [PMID: 24666416]
[http://dx.doi.org/10.1007/s00405-013-2444-x] [PMID: 23580032]
[http://dx.doi.org/10.18632/oncotarget.22618] [PMID: 29312593]
[http://dx.doi.org/10.3727/096504017X15009419625178] [PMID: 28762328]