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1、乙烷硒啉对小鼠体内移植性肝癌(H22)和Lewis肺癌的抗肿瘤作用【摘要】目的观察乙烷硒啉对小鼠移植性肝癌(H22)和Lewis肺癌的抗肿瘤作用,并探讨其可能的抗肿瘤机制。方法建立小鼠体内移植性肝癌(H22)和Lewis肺癌模型,每种属60只,分别设为5组:阴性对照、阳性对照(CTX)和乙烷硒啉3个剂量组,每组12只。于接种肿瘤第2天至第8天5组分别连续腹腔注射5g/L羧甲基纤维素钠溶液、60mg/kgCTX及25、12.5、6.3mg/kg乙烷硒啉。停药3d后(第11天)每组处理一半动物,计算抑瘤率,并用
2、流式细胞仪观察其对细胞周期的影响;另一半动物观察生命延长率。结果乙烷硒啉在25、12.5、6.3mg/kg剂量下对小鼠肝癌H22移植瘤的抑瘤率分别为52.5%、43.6%和30.2%,生命延长率分别为56.6、38.7%和14.2%;对小鼠Lewis肺癌的抑瘤率分别为43.8%、29.6%和18.9%,生命延长率分别为47.3%、17.9%和6.3%。乙烷硒啉各剂量组肿瘤细胞凋亡率明显高于对照组(P<0.05),且25.0mg/kg组出现S期阻滞(P<0.05)。结论乙烷硒啉对小鼠移植性肝癌(H
3、22)和Lewis肺癌具有抗肿瘤作用,且随剂量的增加其抑制肿瘤作用显著增强。其抗肿瘤作用可能是通过诱导细胞凋亡,同时干扰肿瘤细胞生长周期,导致S期阻滞而实现的。【关键词】乙烷硒啉;H22肝癌株;Lewis肺癌株;流式细胞仪ABSTRACT:ObjectiveToobservetheantitumoreffectof9ethaselenontransplantedlivercancer(H22)andLewislungcancermice.MethodsThetransplantedlivercancer(
4、H22)andLewislungcancermicemodelswereestablished.Eachgenusconsistedof60mice,whichweredividedintocontrol,CTX,andthreeethaselendosegroups,respectively,with12miceineach.Intraperitonealinjection(ip.)ofthreedosageswasperformedonceadaythroughtheabdominalwallsepar
5、ately,fromthesecondtotheeighthdayaftercancerwastransplanted.Ontheeleventhday,sixmiceineachgroupwerekilledtocalculatethetumorinhibitionratioandobservethecellcyclebyflowcytometry,andtheotherswereobservedforthelifeextensionratio.ResultsWhenethaselenwasgivenat
6、thedosageof25,12.5and6.3mg/kg,thetumorinhibitionratiowas52.5%,43.6%and30.2%,andthelifeextensionratiowas56.6%,38.7%and14.2%inthetransplantedlivercancer(H22)mice,respectively.Thetumorinhibitionratiowas43.8%,29.6%and18.9%,andthelifeextensionratiowas47.3%,17.9
7、%and6.3%inthetransplantedLewislungcancermice,respectively.Comparedwiththatofthecontrol,theapoptosisratiowasobviouslyincreasedineachgroup,andtherewasobviouslyinducedSphasearrestin25.0mg/kg(P<0.05).ConclusionEthaselenhasanantitumoreffectonthetransplanted
8、livercancer(H22)andLewislung9cancermice,andasdosageisincreased,theeffectisenhanced.Themechanismmaybeaccomplishedthroughinterferingtumorcellgrowthcycle,Sphasearrestandapoptosis.KEYWORDS:ethaselen;H22livercance