tsa對(duì)肺腺癌細(xì)胞株a549細(xì)胞凋亡的影響

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1、TSA對(duì)肺腺癌細(xì)胞株A549細(xì)胞凋亡的影響腫瘤2006年11月第26卷第11期TumorVo1.26,No.11,Nov.2006TSA對(duì)肺腺癌細(xì)胞株A549細(xì)胞凋亡的影響B(tài)asicResearch?基礎(chǔ)研究姜淑娟,尚建強(qiáng),張嵩,楊艷娜,賈奠婷,JIANGShi—wen.(1.山東省立醫(yī)院呼吸科,濟(jì)南250021;2.MayoClinic,Rochester,Minnesota,55902USA)[摘要]目的:探討組蛋白脫乙?；敢种苿┣乓志谹(trichostatinA,TSA)對(duì)A549肺腺癌細(xì)胞凋亡的影響.方法:AnnexinV和Hoechst染色法檢

2、測(cè)細(xì)胞凋亡;流式細(xì)胞儀分析細(xì)胞周期;Westernblot檢測(cè)凋亡信號(hào)通路中caspase-8,caspas9活化及多聚ADP核糖聚合酶(PARP)裂解情況.結(jié)果:TSA可誘導(dǎo)細(xì)胞凋亡,主要使細(xì)胞積聚在Gz/M期,且呈濃度依賴性.Westernblot檢測(cè)表明TSA誘導(dǎo)了A549肺腺癌細(xì)胞caspase-8,caspase~9裂解活化及PARP裂解,且隨TSA作用時(shí)間延長(zhǎng)而逐步升高.結(jié)論:TSA誘導(dǎo)A549細(xì)胞凋亡中caspase-8,caspase一9介導(dǎo)caspase~3的活化,TSA通過caspase級(jí)聯(lián)反應(yīng)誘導(dǎo)A549細(xì)胞凋亡.[關(guān)鍵詞]肺腫瘤;曲古抑菌

3、素A;細(xì)胞凋亡;A549細(xì)胞[中圖分類號(hào)]R734.3[文獻(xiàn)標(biāo)識(shí)碼]A[文章編號(hào)]1000—7431(2006)11—1007—04EffectoftrichostatinAonapoptosisoflungepithelialcarcinomaA549cellsJIANGShu—juan,SHANGJian—qiang,ZHANGSong,YANGYa—na,JIAYan-ting,JIANGShi—wen.(1.Depart—mentofRespiratoryDisease,ShandongProvincialHospital,Jinan250021,Chi

4、na;2.MayoClinic,Rochester,Minnesota,55902,USA)I-ABSTRACT]Objective:TostudytheeffectofhistonedeacetylaseinhibitortrichostatinA(TSA)onapoptosisoflungepitheli—alcarcinomaA549cellline.Methods:ApoptosiswasobservedbyAnnexinVandHoechststaining.Thecellcyclewasanalyzedbyflowcytometry.Activati

5、onofcaspase-8andcaspase~9andcleavageofpoly(ADP—ribose)polymerase(PARP)weredetectedbyWesternblot.Results:TSAinducedapoptosisofA549cellsandarrestedcellsinG2/Mphaseinadose—dependentmanner.WesternblotanalysisshowedthatTSAinducedactivationofcaspase一8andcaspase一9andcleavageofPPARofA549cell

6、sinatime-dependentmanner.Conclusions:TSAinducedcaspase-8andcaspase~9一mediatedcaspase~3activationduringapoptosisofA549cells.TSAinducestheapoptosisofA549cellsviacaspasecascadepathway.VKEYWORDS~Iungneoplasms;TrichostatinA;Apoptosis;A549cells[Tumor,2006,26(11):1007—1010]肺癌是所有惡性腫瘤調(diào)整病死率中增長(zhǎng)

7、最快,危害最大的惡性腫瘤之一.75肺癌患者在確診時(shí)已屬IIIb和IV期,失去了手術(shù)機(jī)會(huì)n],因此,尋找殺傷肺癌細(xì)胞的新藥及探討其作用機(jī)制是目前研究的熱點(diǎn)之一.曲古抑菌素A(trichostatinA,TSA)是組蛋白脫乙酰化酶1(histonedeacetylaseHDAC1)抑制劑,可特異性地抑制哺乳動(dòng)物組蛋白脫乙酰酶,使高度?；慕M蛋白積累,激活基因表達(dá),抑制細(xì)胞增殖,引起細(xì)胞分化或調(diào)亡,是目前國(guó)際上公認(rèn)的研究?；瘜?duì)細(xì)胞影響的可靠模式.TSA可通過抑制組蛋白脫?；甘鼓[瘤細(xì)胞酰基化蛋白質(zhì)增加,導(dǎo)致細(xì)胞生長(zhǎng)抑制和調(diào)亡,可選擇性激活培養(yǎng)腫瘤細(xì)胞的許多基因,改

8、變其基因的表達(dá).本實(shí)驗(yàn)研