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1、鬼臼毒衍生物誘導(dǎo)人肺腺癌A549細(xì)胞凋亡【關(guān)鍵詞】鬼臼毒素；肺腫瘤；腺癌；,細(xì)胞凋亡；抗原,CD95；基因,Bcl ApoptosisinhumanlungadenocarcinomacelllineA549byderivativeofpodophyllotoxin 【Abstract】AIM:TostudytheapoptosisofhumanlungadenocarcinomaA549cellsinducedbyCN2,aderivativeofpodophyllotoxin,andtoobtaininsightsintoitsmolecul
2、armechanismofaction.METHODS:MTTassay,electronmicroscopy,DNAagarosegelelectrophoresisandcellcycleananlysiswereusedtoexamineapoptosisinA549cells.ExpressionsofBcl2,caspase3andFasproteinsweremeasuredwithflowcytometry.RESULTS:CN2wasdemonstratedtoexertantiproliferativeactivityinadose
3、andtimedependentmanner.IC50ofA549after24,48,72hexposuretoCN2was108.20,41.28,20.67mg/L,respectively.Typicalapoptoticmorphologicalchangeswereobservedbyelectronmicroscope;agarosegelelectrophoresisshowedanevidentDNAfragmentation;cellcycleanalysisindicatedanincreasedSphaseproportion
4、,aswellasanapparentS/G2phasearrest.CN2decreasedBcl2proteinexpression10(P<0.05)dramatically.Fasproteinexpressionshowednoobviouschanges.CONCLUSION:CN2couldinhibitthegrowthofA549cellsviatheinductionofS/G2phasearrest,whichisprobablyassociatedwiththedecreasedBcl2expressionandcell
5、cyclearrest. 【Keywords】podophyllotoxin;lungneoplasms;adenocarcinoma;apoptosis;antigens,CD95;genes,Bcl2 【摘要】目的：研究鬼臼素衍生物CN2對(duì)人肺腺癌細(xì)胞A549的凋亡誘導(dǎo)作用，并對(duì)其分子機(jī)制進(jìn)行初步探討.方法：采用四甲基偶氮唑藍(lán)(MTT)比色法、電子顯微鏡、DNA瓊脂糖凝膠電泳和細(xì)胞周期分析法檢測(cè)A549細(xì)胞凋亡；采用流式細(xì)胞術(shù)(FCM)測(cè)定細(xì)胞Bcl2,Fas及caspase3蛋白表達(dá)水平.結(jié)果：CN2對(duì)A549細(xì)胞增殖具有明顯的劑量和時(shí)間依
6、賴的抑制作用，24,48,72hIC50分別為108.20,41.28,20.67mg/L，電鏡觀察呈現(xiàn)典型的凋亡形態(tài)改變；DNA電泳可見(jiàn)明顯的梯狀條帶；細(xì)胞周期分析顯示S期細(xì)胞數(shù)明顯增多，出現(xiàn)S/G2期阻滯；CN2能顯著降低Bcl2蛋白表達(dá)(P<0.05)；Fas蛋白表達(dá)水平未見(jiàn)明顯變化.結(jié)論：CN2通過(guò)誘導(dǎo)A549細(xì)胞發(fā)生S/G2期阻滯而抑制其增殖，其機(jī)制可能與下調(diào)Bcl2表達(dá)及阻滯細(xì)胞周期有關(guān).10 【關(guān)鍵詞】鬼臼毒素；肺腫瘤；腺癌；細(xì)胞凋亡；抗原，CD95；基因，Bcl2 0引言 鬼臼毒類化合物用于民間藥物治療已有較長(zhǎng)的歷史，目前
7、臨床上比較成熟的藥物依托泊甙（etoposide,vp16）和替尼泊甙（teniposide,VM26）對(duì)小細(xì)胞肺癌有良好的療效.但由于此類化合物水溶性差、抗瘤譜窄及具有較嚴(yán)重的骨髓抑制作用等不足使其應(yīng)用受到限制［1］.自旋標(biāo)記化合物CN2是一種引入了氮氧自由基的去甲表鬼臼毒（4β［2”,2,6”,6四甲基1”,2”,5”,6”四氫吡啶氮氧自由基4”西佛堿丁基］4脫氫4去甲表鬼臼毒,英文名為4β［2”,2,6”,6tetramethyl1”,2”,5”,6”tetrahydropyridinenitroxyl4”shiffsbase］4deoxy4d
8、emethylepipodophyllotoxin），其同類化合物可顯著抑制小鼠移植性腫瘤白血病P388和實(shí)
