摘要
宫颈癌是全世界妇女癌症死亡的第四大原因。由于宫颈癌的高发病率和高死亡率,对有效的诊断、治疗和预防制剂的需求尚未得到满足。目前,晚期转移性宫颈癌的首选治疗策略包括手术、放疗和化疗。然而,宫颈癌对化疗逐渐产生耐药性,从而降低其疗效。在过去的几十年里,植物化学物质,即从植物中产生的化合物的总称,因其在预防宫颈癌方面的作用而受到关注。这种在预防子宫颈癌中的作用已经引起了人们对水果和蔬菜的药用特性的关注。目前正在评估植物化学物质阻断参与宫颈癌发生的蛋白质和对宫颈癌的化学耐药性的能力。对顺铂、阿霉素和5-氟尿嘧啶等癌症药物的耐药已成为药物化疗的一个重要限制。然而,顺铂与其他植物化学物质的联合已被认为是抑制顺铂耐药性的一种有希望的替代方法。由于植物化学物质具有抗氧化、抗炎和抗增殖的潜能,对包括宫颈癌在内的许多癌症具有很好的化学预防和化疗作用。此外,这种植物化学物质通过上下调节各种蛋白质来调节细胞信号通路的能力已被认为具有治疗潜力。在宫颈癌细胞中,植物化学物质还具有广泛的生物学功能,包括细胞周期阻滞、诱导凋亡、抑制侵袭和迁移等。大量研究揭示了不同信号蛋白及其信号通路在宫颈癌发病机制中的重要作用。在此,我们综述了几种膳食植物化学物质通过调节各种分子靶点来改变致癌作用的能力。
关键词: 宫颈癌,癌变,氧化应激,化学抗性,植物化学物质,细胞毒性,化疗,凋亡。
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[http://dx.doi.org/10.1080/21645515.2016.1239669] [PMID: 28409676]
[http://dx.doi.org/10.1016/S1470-2045(10)70230-8] [PMID: 20952254]
[http://dx.doi.org/10.1016/j.vaccine.2012.07.055] [PMID: 23199955]
[http://dx.doi.org/10.1016/j.bbadis.2011.10.005] [PMID: 22019724]
[http://dx.doi.org/10.7314/APJCP.2012.13.6.2687] [PMID: 22938442]
[http://dx.doi.org/10.1007/s13277-013-1302-1] [PMID: 24272199]
[http://dx.doi.org/10.1207/s15327914nc4902_1] [PMID: 15489203]
[http://dx.doi.org/10.1002/ijc.30716] [PMID: 28369882]
[http://dx.doi.org/10.1016/j.vaccine.2006.05.031] [PMID: 16950018]
[http://dx.doi.org/10.1158/1055-9965.EPI-10-0576] [PMID: 20833971]
[http://dx.doi.org/10.1111/jog.13248] [PMID: 28165175]
[http://dx.doi.org/10.1093/emph/eov003] [PMID: 25634317]
[http://dx.doi.org/10.1016/j.vaccine.2012.06.083] [PMID: 23199966]
[http://dx.doi.org/10.1016/j.virol.2004.03.033] [PMID: 15183049]
[http://dx.doi.org/10.1016/j.virol.2010.02.002] [PMID: 20206957]
[http://dx.doi.org/10.1007/978-981-10-5765-6_3]
[http://dx.doi.org/10.1007/s00018-009-8631-7] [PMID: 19183849]
[http://dx.doi.org/10.1016/j.mrrev.2016.09.004] [PMID: 28528686]
[http://dx.doi.org/10.1128/JVI.00330-13] [PMID: 23536685]
[http://dx.doi.org/10.1128/JVI.78.21.11451-11460.2004] [PMID: 15479788]
[http://dx.doi.org/10.1016/j.clinthera.2016.02.007] [PMID: 26926322]
[http://dx.doi.org/10.1016/j.ijrobp.2008.06.1905]
[http://dx.doi.org/10.7314/APJCP.2014.15.19.8007] [PMID: 25338977]
[http://dx.doi.org/10.1371/journal.pone.0084506] [PMID: 24376816]
[http://dx.doi.org/10.1016/S1470-2045(11)70287-X] [PMID: 22075170]
[PMID: 25811679]
[http://dx.doi.org/10.4161/hv.29532] [PMID: 25424918]
[http://dx.doi.org/10.1158/1940-6207.CAPR-13-0203] [PMID: 24189371]
[http://dx.doi.org/10.1016/S1470-2045(15)00414-3] [PMID: 26652797]
[http://dx.doi.org/10.3390/ph14020157] [PMID: 33673021]
[http://dx.doi.org/10.1016/j.cca.2020.01.035] [PMID: 32017926]
[http://dx.doi.org/10.1016/j.phymed.2020.153402] [PMID: 33203590]
[http://dx.doi.org/10.3390/ijms22168812] [PMID: 34445518]
[http://dx.doi.org/10.1016/j.arabjc.2021.103106]
[http://dx.doi.org/10.1016/j.canlet.2010.12.021] [PMID: 21306823]
[http://dx.doi.org/10.1016/j.vaccine.2008.05.064] [PMID: 18847553]
[PMID: 12460913]
[http://dx.doi.org/10.1007/s11262-014-1164-7] [PMID: 25823917]
[http://dx.doi.org/10.1126/science.1229934] [PMID: 23393263]
[http://dx.doi.org/10.1038/sj.onc.1202223] [PMID: 9881696]
[http://dx.doi.org/10.1038/sj.onc.1209429] [PMID: 16462759]
[http://dx.doi.org/10.1016/0092-8674(93)90384-3] [PMID: 8221889]
[http://dx.doi.org/10.1128/JVI.75.16.7583-7591.2001] [PMID: 11462030]
[http://dx.doi.org/10.1073/pnas.98.3.1218] [PMID: 11158620]
[http://dx.doi.org/10.1128/JVI.76.20.10559-10568.2002] [PMID: 12239337]
[http://dx.doi.org/10.1038/nrc2886] [PMID: 20592731]
[http://dx.doi.org/10.1016/j.virol.2008.11.017] [PMID: 19081593]
[http://dx.doi.org/10.1111/j.1349-7006.2007.00546.x] [PMID: 17645777]
[http://dx.doi.org/10.1002/rmv.605] [PMID: 19156753]
[http://dx.doi.org/10.1186/1868-7083-4-13] [PMID: 22938091]
[http://dx.doi.org/10.1038/nrc3536] [PMID: 23760023]
[http://dx.doi.org/10.1002/ijc.11691] [PMID: 14750163]
[http://dx.doi.org/10.1038/onc.2008.224] [PMID: 18758479]
[http://dx.doi.org/10.1126/science.284.5415.770] [PMID: 10221902]
[http://dx.doi.org/10.1007/BF02913333] [PMID: 23105702]
[http://dx.doi.org/10.1007/s11670-010-0087-7]
[http://dx.doi.org/10.1155/2018/5315816] [PMID: 30225270]
[http://dx.doi.org/10.1016/j.canlet.2016.03.042] [PMID: 27037062]
[http://dx.doi.org/10.1016/j.biocel.2006.07.001] [PMID: 16978905]
[http://dx.doi.org/10.1007/s12291-014-0446-0] [PMID: 25646037]
[http://dx.doi.org/10.1042/BST0351147]
[http://dx.doi.org/10.1016/j.biopha.2018.04.126] [PMID: 29710659]
[http://dx.doi.org/10.1016/j.bbagen.2014.12.016] [PMID: 25534611]
[http://dx.doi.org/10.2217/fvl.10.73] [PMID: 21318095]
[http://dx.doi.org/10.1038/nrc2981] [PMID: 21258394]
[http://dx.doi.org/10.3390/v5020708] [PMID: 23403708]
[http://dx.doi.org/10.14740/wjon1088w] [PMID: 29581812]
[http://dx.doi.org/10.1016/S0009-8981(02)00300-5] [PMID: 12417105]
[http://dx.doi.org/10.1080/10258140290018685] [PMID: 12186759]
[http://dx.doi.org/10.1016/j.freeradbiomed.2003.12.010] [PMID: 14990352]
[http://dx.doi.org/10.1038/sj.onc.1203174] [PMID: 10557108]
[http://dx.doi.org/10.1155/2014/190860] [PMID: 24701032]
[http://dx.doi.org/10.1155/2017/4180703] [PMID: 28261610]
[http://dx.doi.org/10.1042/BST20150069] [PMID: 26551713]
[http://dx.doi.org/10.1016/j.cbi.2005.12.009] [PMID: 16430879]
[http://dx.doi.org/10.1074/jbc.274.13.8516] [PMID: 10085084]
[http://dx.doi.org/10.1074/jbc.M311370200] [PMID: 14688260]
[http://dx.doi.org/10.1186/1477-3163-5-14] [PMID: 16689993]
[http://dx.doi.org/10.1016/j.phrs.2009.01.017] [PMID: 19429468]
[http://dx.doi.org/10.18632/oncotarget.19048] [PMID: 28938696]
[http://dx.doi.org/10.18632/oncotarget.14021] [PMID: 28008141]
[http://dx.doi.org/10.1023/A:1016290704772] [PMID: 7724492]
[PMID: 10442356]
[http://dx.doi.org/10.1016/j.eupc.2004.12.012] [PMID: 15878560]
[http://dx.doi.org/10.1111/j.1365-2559.1993.tb00135.x] [PMID: 8514278]
[http://dx.doi.org/10.2319/091609-522.1] [PMID: 20936960]
[http://dx.doi.org/10.3389/fphar.2019.00715] [PMID: 31417401]
[http://dx.doi.org/10.1002/jcp.29703] [PMID: 32324275]
[http://dx.doi.org/10.1016/j.canlet.2009.04.033] [PMID: 19464787]
[http://dx.doi.org/10.1007/s12038-018-9743-8] [PMID: 29872014]
[PMID: 31983099]
[http://dx.doi.org/10.1016/j.biopha.2017.10.147] [PMID: 29107932]
[http://dx.doi.org/10.1002/ptr.5932] [PMID: 29044755]
[http://dx.doi.org/10.1016/j.biopha.2016.04.056] [PMID: 27470354]
[http://dx.doi.org/10.1038/srep36594] [PMID: 27824155]
[http://dx.doi.org/10.1007/s10529-016-2102-7] [PMID: 27099069]
[http://dx.doi.org/10.3802/jgo.2019.30.e77] [PMID: 31328459]
[PMID: 30610802]
[PMID: 30606896]
[http://dx.doi.org/10.4103/0973-1482.204899] [PMID: 31898650]
[http://dx.doi.org/10.12659/MSM.898658] [PMID: 27941714]
[http://dx.doi.org/10.1097/CAD.0000000000000424] [PMID: 27557139]
[PMID: 21725610]
[PMID: 27467006]
[http://dx.doi.org/10.1021/acs.jafc.7b00095] [PMID: 28230361]
[http://dx.doi.org/10.1371/journal.pone.0191523] [PMID: 29420562]
[http://dx.doi.org/10.2147/DDDT.S187776] [PMID: 30587932]
[http://dx.doi.org/10.3892/or.2016.4800] [PMID: 27176229]
[http://dx.doi.org/10.1016/j.biopha.2017.11.022] [PMID: 29169726]
[http://dx.doi.org/10.1073/pnas.92.6.1831] [PMID: 7892186]
[http://dx.doi.org/10.1124/mol.114.094037] [PMID: 25217495]
[http://dx.doi.org/10.1186/1476-4598-10-39] [PMID: 21496227]
[PMID: 17970084]
[http://dx.doi.org/10.7150/jca.22427] [PMID: 29721044]
[http://dx.doi.org/10.1002/ptr.6687] [PMID: 32364634]
[http://dx.doi.org/10.1016/j.canlet.2014.05.005] [PMID: 24831030]
[http://dx.doi.org/10.3892/or.2012.2024] [PMID: 22965493]
[http://dx.doi.org/10.3390/biom9090494] [PMID: 31527550]
[http://dx.doi.org/10.1002/mnfr.201700965] [PMID: 29468815]
[http://dx.doi.org/10.1021/jf2006358] [PMID: 21702500]
[http://dx.doi.org/10.3389/fphar.2021.673103] [PMID: 34393773]
[http://dx.doi.org/10.3892/ol.2018.8428] [PMID: 29805614]
[PMID: 30783417]
[http://dx.doi.org/10.1016/j.canep.2010.09.008] [PMID: 20956097]
[http://dx.doi.org/10.3390/ijms17091530]
[http://dx.doi.org/10.1155/2015/412149]
[http://dx.doi.org/10.2174/1871520620999200818154456]
[PMID: 19035312]
[http://dx.doi.org/10.1007/s12032-021-01456-3] [PMID: 33474656]
[http://dx.doi.org/10.1016/j.bbadis.2008.07.002] [PMID: 18675902]
[http://dx.doi.org/10.1016/j.prp.2018.12.010] [PMID: 30567634]
[http://dx.doi.org/10.3892/or.2013.2741] [PMID: 24065213]
[http://dx.doi.org/10.1371/journal.pone.0120045] [PMID: 25786122]
[http://dx.doi.org/10.1016/S0014-2999(03)01976-9] [PMID: 12892828]
[http://dx.doi.org/10.1016/j.lfs.2018.03.003] [PMID: 29505783]
[http://dx.doi.org/10.1007/s10565-010-9174-2] [PMID: 20717715]
[http://dx.doi.org/10.4161/cbt.27223] [PMID: 24335512]
[http://dx.doi.org/10.1016/j.biopha.2018.08.060] [PMID: 30257408]
[PMID: 30431140]
[http://dx.doi.org/10.1186/s12906-016-1280-0] [PMID: 27586579]
[http://dx.doi.org/10.3390/molecules22081299] [PMID: 28777347]
[http://dx.doi.org/10.1002/mc.20031]
[http://dx.doi.org/10.1007/s11033-013-2660-x] [PMID: 24065519]
[http://dx.doi.org/10.1111/j.1582-4934.2011.01346.x] [PMID: 21609393]
[http://dx.doi.org/10.1016/j.semcancer.2020.06.014]
[http://dx.doi.org/10.1016/j.biopha.2018.10.107] [PMID: 30551389]
[http://dx.doi.org/10.1007/s10555-010-9239-y] [PMID: 20798979]
[http://dx.doi.org/10.3390/ijms22073571] [PMID: 33808235]
[http://dx.doi.org/10.1016/j.toxlet.2019.08.006] [PMID: 31415786]
[http://dx.doi.org/10.3389/fonc.2020.01039] [PMID: 32766133]
[http://dx.doi.org/10.1245/s10434-015-4555-7] [PMID: 25916979]
[http://dx.doi.org/10.1002/stem.3157] [PMID: 32100928]
[http://dx.doi.org/10.1007/s00280-018-03766-2] [PMID: 30631898]
[http://dx.doi.org/10.1038/s41419-020-2735-2] [PMID: 32661236]
[http://dx.doi.org/10.1038/cddis.2014.297] [PMID: 25118927]
[PMID: 29151072]
[http://dx.doi.org/10.3892/or.2015.3769] [PMID: 25634668]
[http://dx.doi.org/10.18632/oncotarget.2377] [PMID: 25193857]
[http://dx.doi.org/10.1038/cddis.2017.393] [PMID: 28880275]
[http://dx.doi.org/10.3892/mmr.2017.7665] [PMID: 28990097]
[http://dx.doi.org/10.1093/carcin/bgz168] [PMID: 31584624]
[http://dx.doi.org/10.3802/jgo.2020.31.e28] [PMID: 31912682]
[http://dx.doi.org/10.1016/j.omto.2020.05.008]
[http://dx.doi.org/10.18632/oncotarget.25748] [PMID: 30093972]
[http://dx.doi.org/10.12659/MSM.906413] [PMID: 29650944]
[http://dx.doi.org/10.1111/cas.13275] [PMID: 28498637]
[http://dx.doi.org/10.1002/mc.22205] [PMID: 25154814]
[http://dx.doi.org/10.3892/ol.2016.5160] [PMID: 27895735]
[http://dx.doi.org/10.1186/s13000-015-0404-z] [PMID: 26411419]
[http://dx.doi.org/10.1007/s13277-013-0794-z] [PMID: 23595222]
[http://dx.doi.org/10.3892/or.2014.3401] [PMID: 25119492]
[http://dx.doi.org/10.2217/bmm-2016-0056] [PMID: 27347840]
[http://dx.doi.org/10.1155/2016/7981397] [PMID: 28053694]
[http://dx.doi.org/10.1002/jcp.26900] [PMID: 30078217]
[http://dx.doi.org/10.18632/oncotarget.22133] [PMID: 29228621]
[http://dx.doi.org/10.3892/or.2012.1841] [PMID: 22665077]
[http://dx.doi.org/10.1007/s13277-015-4526-4] [PMID: 26662956]
[http://dx.doi.org/10.3892/ol.2018.8256] [PMID: 29731891]
[http://dx.doi.org/10.1002/jcb.27886] [PMID: 30390323]
[PMID: 32134040]
[http://dx.doi.org/10.1097/CAD.0b013e328347181a] [PMID: 21642840]
[http://dx.doi.org/10.3390/molecules24213979] [PMID: 31684176]
[http://dx.doi.org/10.1007/s00432-016-2235-z] [PMID: 27613187]
[PMID: 25972998]
[http://dx.doi.org/10.3390/biom10070994] [PMID: 32630700]
[http://dx.doi.org/10.1002/mnfr.201000560] [PMID: 21595016]
[http://dx.doi.org/10.1371/journal.pone.0029169] [PMID: 22216199]
[http://dx.doi.org/10.1016/j.bcp.2005.01.022] [PMID: 15826605]
[http://dx.doi.org/10.1016/j.cbi.2013.07.003] [PMID: 23867903]