REGgamma基因对乳腺癌细胞MCF-7增殖和凋亡的影响

目的:探讨蛋白酶体激活因子REGgamma(REGγ)基因对乳腺癌细胞MCF-7增殖和凋亡的作用.方法:构建真核表达重组体PcDNA3.1-REGγ,通过脂质体转染将REGγ基因导入MCF-7,以G418(800mg/L)连续筛选获得稳定高表达REGγ基因的细胞株,以转染空载体和未转染细胞作为对照.分别利用MTT法及免疫细胞化学方法检测各组细胞PCNA的表达分析REGγ基因对细胞增殖的影响;以Caspase-3分光光度法及AnnexinV-FITC的流式细胞仪(FCM)来检测细胞凋亡的变化;以透射电镜(TEM)观察细胞超微结构的改变.结果:获得稳定转染且高表达REGγ的细胞株.经Western Blot检测转染REGγ基因的细胞(实验组),其REGγ蛋白表达明显高于对照组细胞(P＜0.05);未转染组、空载体组和实验组细胞的倍增时间分别为34.6、35.1、26.7h.提示实验组细胞倍增时间缩短;MTT法绘制生长曲线提示实验组细胞生长明显加速;免疫细胞化学检测PCNA结果显示,未转染组、空载体组和实验组细胞的染色灰度值分别为89.61±14.32、87.95±16.38、133.47±8.14,表明实验组细胞PCNA表达明显增强(P＜0.01);Caspase-3分光光度法检测显示,实验组细胞的OD值普遍低于对照组(P＜0.05);Annexin V-FITC的FCM检测显示,实验组细胞的凋亡率明显低于对照组(P＜0.01);TEM观察实验组细胞表现为核仁肥大,线粒体、高尔基体丰富或扩张,未见凋亡小体形成.结论:REGγ基因具有促进乳腺癌MCF-7细胞增殖并抑制其凋亡的作用.     

PUMA基因转染乳腺癌MCF-7细胞增强表柔比星致凋亡敏感性的研究

  目的  探讨PUMA基因转染是否增强乳腺癌MCF-7细胞对表柔比星致凋亡的敏感性。   方法  应用脂质体介导重组真核表达载体PUMA-pCDNA3和空载体pCDNA3质粒瞬时转染至乳腺癌MCF-7细胞中, G418筛选阳性细胞。将系列浓度(0.01~100μmol/L)的表柔比星分别作用于MCF-7、MCF-7/PUMA和MCF-7/pCDNA3细胞72 h, MTT法测定各组细胞的存活率并计算IC50, FCM、TUNEL法检测细胞凋亡情况, Western blotting检测各组细胞PUMA蛋白表达的变化。   结果  MCF-7、MCF-7/PUMA和MCF-7/pCDNA3细胞的表柔比星IC50分别为(13±1.4)、(1.8±0.2)和(10.7±1.3)μmol/L, MCF-7/PUMA细胞对表柔比星作用的敏感性增加了7.2倍。表柔比星以剂量依赖方式诱导MCF-7细胞凋亡, 但对MCF-7/PUMA细胞所诱导的凋亡比MCF-7和MCF-7pCDNA3更明显。低浓度表柔比星(0.1μmol/L)轻微引起MCF-7/pCDNA3[(1.15±0.26)%]和MCF-7细胞凋亡[(0.9±0.24)%], 但能诱导MCF-7/PUMA细胞明显凋亡[(6.44±1.46)%]; 高浓度表柔比星(1μmol/L)诱导各组细胞凋亡, 但表柔比星MCF-7/PU MA细胞凋亡率[(35.47±9.36)%]明显高于MCF-7[(12.6±3.73)%]和MCF-7/pCDNA3细胞[(15.2±5.17)%], 差异均有统计学意义(P < 0.01);FCM和TUNEL方法检测显示相同的结果。PUMA蛋白在MCF-7/PUMA细胞中的表达明显高于MCF-7和MCF-7/pCD NA3细胞。   结论  PUMA基因稳定转染明显地增强了乳腺癌MCF-7细胞增强表柔比星致凋亡作用的敏感性。      

转染野生型p53对乳腺癌细胞所致细胞凋亡的研究

为研究ｐ５３对乳腺癌细胞增殖和凋亡的影响,用重组人野生型ｐ５３全长ｃＤＮＡ的逆转录病毒载体转染Ｂｃａｐ３７细胞,观察其增殖的凋亡变化。方法 应用Ｎｏｒｔｈｅｒｎ ｂｌｏｔｔｉｎｇ和Ｗｅｓｔｅｒｎ ｂｌｏｔｔｉｎｇ检测Ｂｃａｐ３７细胞表达变化,流式细胞仪计数检测细胞增殖及周期变化,ＭＴＴ及苔盼兰计数观察紫外线刺激后细胞存活率差异,ＤＮＡ末端原位标记技术检测细胞凋亡变化。     

IL-23基因转染小鼠乳腺癌细胞的体内外促凋亡作用研究

目的:将小鼠IL-23基因转染小鼠乳腺癌细胞MA-891,检测该细胞在体内外的凋亡变化,探讨IL-23抗肿瘤作用机制.方法:应用逆转录病毒载体(LXSN)将含 IL-23 基因质粒经ψ2(亲嗜性)和PA317(双嗜性) 2种细胞包装,G418筛选获得携带 IL-23 基因的病毒,后者转染MA-891细胞,经G418筛选后获得IL-23/MA-891阳性克隆.用ELISA法检测IL 23/MA-891细胞分泌IL-23的能力,用MTT比色法检测细胞体外增殖能力.小鼠皮下接种转染IL-23/MA-891细胞,观察其体内致瘤性变化;用流式细胞术及TUNEL法检测肿瘤细胞凋亡情况;用RT-PCR和Western 印迹法检测肿瘤组织Fas和survivin的表达.结果: IL-23 基因成功转染MA-891细胞,获得了IL-23高表达细胞IL-23/MA-891.转染 IL-23 基因不影响MA-891细胞的体外生长和细胞凋亡,但体内 IL-23 基因转染组肿瘤生长明显受到抑制,肿瘤组织细胞凋亡率增高( P <0.01),细胞表面Fas的表达水平明显增加( P <0.01),survivin表达水平明显降低( P <0.01).结论:转染小鼠 IL-23 基因后对小鼠乳腺癌细胞MA-891的体外凋亡无影响,但在体内 IL-23 可能通过降低survivin表达和上调Fas表达,诱导细胞凋亡而产生抗肿瘤作用.     

MST1 基因对乳腺癌细胞MCF-7增殖与凋亡的影响

目的:探讨 MST1 ( mammalian sterile 20-like kinase 1)基因对人乳腺癌细胞MCF-7增殖与凋亡的影响.方法:构建含有标签蛋白FLAG的MST1质粒pCMV-FLAG-MST1;将构建好的pCMV-FLAG-MST1质粒在脂质体lipofectamine 2000的介导下转染MCF-7细胞,通过Western 印迹法分析MST1在MCF-7中的表达情况;分别在转染后12、24、36和48 h通过MTT法观察MST1对细胞增殖的影响;转染后36 h加入5-溴-2'脱氧尿嘧啶(bromodeoxy uridine,BrdU),通过其掺入比率显示MST1对细胞增殖的影响;转染后36 h加入顺铂,作用14 h后通过Annexin Ⅴ检测其对细胞凋亡的影响.结果:成功构建 pCMV-FLAG-MST1质粒;MTT及BrdU检测显示,转染pCMV-FLAG-MST1质粒后 MCF 7细胞增殖明显受到抑制;Annexin Ⅴ检测结果提示,高表达MST1后,细胞的凋亡率相对增高.结论:在乳腺癌细胞MCF 7中高表达MST1,不仅可以抑制细胞增殖,还可以促进细胞凋亡.     

MSTI基因对乳腺癌细胞MCF-7增殖与凋亡的影响

目的：探讨MST1（mammalian sterile 20-like kinase1）基因对人乳腺癌细胞MCF-7增殖与凋亡的影响。方法：构建含有标签蛋白FLAG的MSTI质粒pCMV-FLAG-MST1；将构建好的pCMV-FLAG-MST1质粒在脂质体lipofectamine2000的介导下转染MCF-7细胞，通过Western印迹法分析MST1在MCF-7中的表达情况；分别在转染后12、24、36和48h通过MTF法观察MST1对细胞增殖的影响；转染后36h加入5-溴-2’脱氧尿嘧啶（bromodeoxy uridine，BrdU），通过其掺入比率显示MST1对细胞增殖的影响；转染后36h加入顺铂，作用14h后通过AnnexinV检测其对细胞凋亡的影响。结果：成功构建pCMV—FLAG-MST1质粒；MTT及BrdU检测显示，转染pCMV—FLAG-MST1质粒后MCF-7细胞增殖明显受到抑制；AnnexinV检测结果提示，高表达MST1后，细胞的凋亡率相对增高。结论：在乳腺癌细胞MCF-7中高表达MST1，不仅可以抑制细胞增殖，还可以促进细胞凋亡。     

抵抗素13肽对人乳腺癌细胞系MCF-7增殖和凋亡的影响

目的研究人工合成抵抗素13肽对人乳腺癌细胞系MCF-7增殖和凋亡的影响。方法根据人抵抗素cDNA编码的氨基酸序列合成抵抗素分子22—34位的13个氨基酸的多肽（CSMEEAINERIQE）。采用MTT法检测细胞的增殖活性,使用流式细胞仪检测细胞凋亡。结果50、500、5000和10000ng／ml抵抗素13肽均能抑制MCF-7细胞生长,抑制率为46％到92％,与对照组相比差异有统计学意义（P〈0．01）。诱导凋亡,四个浓度诱导的细胞凋亡率分别为6．7％、6.9％、7.5％和9．8％,与对照组0．6％的凋亡率比较P〈0．01。结论抵抗素13肽可以抑制乳腺癌细胞系MCF-7的增殖,促进细胞凋亡。     

siRNA封闭BRCAA1基因对乳腺癌细胞MCF-7增殖和Rb基因表达的影响

目的：〖HT5"SS〗 研究siRNA封闭乳腺癌抗原相关基因1(BRCAA1)对乳腺癌细胞MCF7增殖和Rb基因表达的影响。〖HT5W〗方法： 〖HT5"SS〗采用RNAi技术对乳腺癌细胞MCF7细胞BRCAA1基因进行特异性抑制,用阳离子脂质体与化学合成的Predesigned antiBRCAA1 siRNA构建转染复合体,反转染MCF7细胞株48h后提取总RNA,分为未处理(NT)组、阴性对照组、阳性对照组和BRCAA1组,经反转录荧光实时PCR检测BRCAA1和Rb基因mRNA表达情况;检测细胞增殖抑制率。〖HT5W〗结果： 〖HT5"SS〗与阴性对照组相比,siRNA转染MCF7细胞后实验组BRCAA1基因mRNA水平降低了42.3％;Rb基因表达较之阴性对照组上升了11.1％;实验组MCF7细胞增殖抑制率为（81.9±6.1）％,抑制作用明显强于对照组(P<0.05)。〖HT5W〗结论： 〖HT5"SS〗BRCAA1基因的封闭明显抑制了MCF7细胞的增殖,BRCAA1基因与Rb基因可能存在有某种相互拮抗的作用。     

改良消减杂交法克隆人乳腺癌MCF-7细胞凋亡相关基因

目的 克隆人乳腺癌MCF-7肿瘤细胞凋亡相关的基因,分析所克隆基因与凋亡的关系。方法 用全反式维甲酸诱导人乳腺癌MCF-7细胞凋亡,建立肿瘤细胞凋亡模型;运用基于聚合酶链式反应（PCR）的改良消减杂交技术,克隆肿瘤细胞凋亡的相关基因。结果 在筛选出的5个特异表达的基因中,4个是已知基因,1个新基因,在4个已知基因中,3个与凋亡关系密切,其中hsp-90和rb-L3与凋亡的关系文献报道较少。结论 维甲酸所诱导的肿瘤细胞凋亡是一个多基因参与的过程,这种基于PCR的改良消减杂交技术为克隆新基因提供了一个新的方法和思路。     

干扰iASPP基因对转染MCF-7细胞凋亡变化的观察

目的:观察iASPP基因干扰RNA转染乳腺癌细胞MCF-7后的干扰效果及细胞凋亡变化。方法:设计特异性siRNA序列,将序列克隆至PGCsilencerTM H1/Neo/GFP质粒中,用脂质体将重组子转染至MCF-7细胞中,用RT-PCR方法检测i ASPP的表达,蛋白质印迹法检测蛋白表达的变化,流式细胞仪检测细胞凋亡的情况。结果:iASPP干扰质粒转染MCF-7细胞后,iASPP的mRNA表达和蛋白表达减少40%～50%;p53蛋白相对表达量由转染阴性质粒的0.37增加到转染干扰质粒的0.64;细胞凋亡率由原来的17.8%和16.2%分别增加到53.5%和51.3%。结论:抑制内源性i ASPP能有效地恢复乳腺癌细胞MCF-7中p53的抑癌功能,为乳腺癌的治疗提供新的思路。     

阿帕替尼通过抑制糖酵解途径对乳腺癌MDA-MB-231细胞增殖抑制及凋亡的作用

 目的 探讨阿帕替尼体外水平抗乳腺癌作用及其机制。方法 采用CCK-8法检测阿帕替尼对乳腺癌MDA-MB-231细胞的增殖抑制作用；采用Annexin V-FITC/PI凋亡检测试剂盒检测阿帕替尼对乳腺癌MDA-MB-231细胞凋亡的影响；采用乳酸含量检测试剂盒检测阿帕替尼对乳腺癌MDA-MB-231细胞内乳酸产量的影响；采用糖酵解压力试剂盒检测阿帕替尼对乳腺癌细胞MDA-MB-231细胞外酸化速率的影响。结果 阿帕替尼可浓度依赖性地抑制乳腺癌MDA-MB-231细胞体外增殖（P<0.05），作用48 h的半数抑制浓度IC₅₀为1.56 μmol/L；阿帕替尼可浓度依赖性地诱导MDA-MB-231细胞凋亡（P<0.05）；阿帕替尼可浓度依赖性地抑制MDA-MB-231细胞内乳酸产量（P<0.05）；阿帕替尼干预可抑制MDA-MB-231细胞的糖酵解能力值及糖酵解保留值，降低MDA-MB-231细胞外酸化速率（P<0.05）。结论 阿帕替尼可能通过抑制乳腺癌MDA-MB-231细胞的有氧糖酵解效应，进而诱导其凋亡。     

GANT61通过自噬性细胞死亡抑制人乳腺癌MCF-7细胞增殖

 目的 观察Hedgehog通路抑制剂GANT61对人乳腺癌MCF-7细胞的抑制作用。方法 GANT61作用MCF-7细胞后,通过流式细胞术检测细胞死亡;提取处理细胞总RNA和蛋白。分别采用Real-timePCR和Western blot检测Hedgehog通路SHH、Gli1、Gli2及自噬标志物LC3-Ⅱ表达;处理细胞固定后通过电子显微镜观察GANT61诱导的自噬体形态;自噬抑制剂3-MA处理细胞或自噬相关基因atg5 siRNA转染细胞后再用GANT61作用,流式细胞术检测细胞死亡数量。结果 GANT61能明显诱导MCF-7死亡,降低Hedgehog通路SHH、Gli1、Gli2表达水平,提高LC3-Ⅱ蛋白表达,并可诱导MCF-7细胞产生自噬体。3-MA及atg5 siRNA可减弱GANT61诱导的细胞死亡。结论 GANT61通过诱导自噬性细胞死亡机制发挥抗乳腺癌细胞活性。     

bcl-2/bcl-xL反义寡核苷酸对乳腺癌细胞增殖和凋亡的影响

目的　观察靶向bcl 2 /bcl xL基因的反义寡核苷酸 (ASODN )对乳腺癌细胞株MCF 7增殖和凋亡的影响。方法　将bcl 2 /bcl xLASODN及其对照序列通过脂质体转染MCF 7细胞。采用MTT法测定MCF 7细胞增殖 ,荧光显微镜定量检测MCF 7细胞凋亡率。结果　与对照序列相比 ,bcl 2 /bcl xLASODN能抑制MCF 7增殖和诱导其凋亡 (P <0 .0 1)。结论　bcl 2 /bcl xLASODN在乳腺癌治疗方面作为 1种新的化合物值得进一步研究     

Ani-survivin DNAzymes Inhibit Cell Proliferation and Migration in Breast Cancer Cell Line MCF-7

Survivin, a new member of the inhibitor of apoptosis protein (IAP) family, both inhibits apoptosis andregulates the cell cycle. It is overexpressed in breast tumor tissues. In this study, we designed two survivinspecific DNAzymes (DRz1 and DRz2) targeting survivin mRNA. The results showed that DRz1 could decreasethe expression of survivin by nearly 60%. Furthermore, DRz1 significantly inhibited cell proliferation, inducedapoptosis and inhibited migration in MCF-7 cells. In addition, down-regulation of survivin expression wasassociated with increased caspase-3 and -9 activities in MCF-7 cells after 24 h transfection. In our experiments,the efficacy of DRz1 to influence survivin levels and associated effects were better than DRz2. Survivin-DRz1might have anti-tumorigenic activity and may potentially provide the basis for a novel therapeutic interventionin breast cancer treatment.     

Isocryptotanshinone Induced Apoptosis and Activated MAPK Signaling in Human Breast Cancer MCF-7 Cells

Purpose

Isocryptotanshinone (ICTS) is a natural bioactive product that is isolated from the roots of the widely used medical herb Salvia miltiorrhiza. However, few reports exist on the mechanisms underlying the therapeutic effects of ICTS. Here, we report that ICTS has anticancer activity and describe the mechanism underlying this effect.

Methods

The antiproliferative effect of ICTS was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and clonogenic assays. The effect of ICTS on the cell cycle was measured using flow cytometry. Apoptosis was determined by Hoechst 33342 staining, DNA fragmentation assays, and Western blotting for apoptotic proteins. Finally, the effect of ICTS on mitogen-activated protein kinases (MAPKs) was determined by Western blotting.

Results

ICTS significantly inhibited proliferation of MCF-7 and MDA-MB-231 human breast cancer cells, HepG2 human liver cancer cells, and A549 human lung cancer cells in vitro. Among the tested cell lines, MCF-7 cells showed the highest sensitivity to ICTS. ICTS significantly inhibited colony formation by MCF-7 cells. Furthermore, exposure of MCF-7 cells to ICTS induced cell cycle arrest at the G1 phase and decreased mitochondrial membrane potential. Hoechst 33342 staining and Western blot analysis for apoptotic proteins suggested that ICTS induced apoptosis in MCF-7 cells. In addition, ICTS activated MAPK signaling in MCF-7 cells by inducing time- and concentration-dependent phosphorylation of JNK, ERK, and p38 MAPK.

Conclusion

Our results suggest that ICTS inhibited MCF-7 cell proliferation by inducing apoptosis and activating MAPK signaling pathways.     

Momordica cochinchinensis Aril Extract Induced Apoptosis in Human MCF-7 Breast Cancer Cells

Momordica cochinchinensis Spreng (MC) has been used in traditional medicine due to its high carotenoidcontent. The objective of this study was to investigate mechanisms underlying apoptotic effects of MC on humanMCF-7 breast cancer cells. A lycopene-enriched aril extract of MC (AE) showed cytotoxicity and antiestrogenicityto MCF-7 cells. On DAPI staining, AE induced cell shrinkage and chromatin condensation were evident. Withflow cytometric analysis, AE increased the percentage of cells in an early apoptosis stage when compared withthe control group. RT-PCR analysis showed AE to significantly increase the expression of the proapoptotic baxgene without effect on expression of the anti-apoptotic bcl-2 gene. Moreover, AE enhanced caspase 6, 8 and 9activity. Taken together, we conclude that AE of MC fruit has anticancer effects on human MCF-7 breast cancercells by induction of cell apoptosis via both intrinsic and extrinsic pathways of signaling     

乳腺癌MCF-7细胞的分子生物学特征

目的研究乳腺癌MCF-7细胞的分子生物学特征。方法采用甲基化特异性PCR(MSP),对MCF-7细胞进行Stratifin和CyclinD2基因甲基化检测;采用RT-PCR法,检测Stratifin、CyclinD2和Dnmt3b基因的mRNA表达。结果乳腺癌MCF-7细胞系中,Stratifin基因是非甲基化的,mRNA表达水平较高;CyclinD2基因完全甲基化,mRNA表达缺失;Dnmt3b基因呈明显表达。结论 Stratifin和CyclinD2基因的甲基化发生,可能下调其mRNA的转录表达,MCF-7细胞的这些分子生物学特性可为乳腺癌的表观遗传学研究提供一定的参考价值。     

Effects of Rapamycin on Cell Apoptosis in MCF-7 Human Breast Cancer Cells

Background: Rapamycin is an effective anti-angiogenic drug. However, the mode of its action remainsunclear. Therefore, in this study, we aimed to elucidate the antitumor mechanism of rapamycin, hypotheticallyvia apoptotic promotion, using MCF-7 breast cancer cells. Materials and Methods: MCF-7 cells were platedat a density of 15105 cells/well in 6-well plates. After 24h, cells were treated with a series of concentrations ofrapamycin while only adding DMEM medium with PEG for the control regiment and grown at 37oC, 5% CO2and 95% air for 72h. Trypan blue was used to determine the cell viability and proliferation. Untreated andrapamycin-treated MCF-7 cells were also examined for morphological changes with an inverted-phase contrastmicroscope. Alteration in cell morphology was ascertained, along with a stage in the cell cycle and proliferation.In addition, cytotoxicity testing was performed using normal mouse breast mammary pads. Results: Our resultsclearly showed that rapamycin exhibited inhibitory activity on MCF-7 cell lines. The IC50 value of rapamycin onthe MCF-7 cells was determined as 0.4μg/ml (p<0.05). Direct observation by inverted microscopy demonstratedthat the MCF-7 cells treated with rapamycin showed characteristic features of apoptosis including cell shrinkage,vascularization and autophagy. Cells underwent early apoptosis up to 24% after 72h. Analysis of the cell cycleshowed an increase in the G0G1 phase cell population and a corresponding decrease in the S and G2M phasepopulations, from 81.5% to 91.3% and 17.3% to 7.9%, respectively. Conclusions: This study demonstrated thatrapamycin may potentially act as an anti-cancer agent via the inhibition of growth with some morphologicalchanges of the MCF-7 cancer cells, arrest cell cycle progression at G0/G1 phase and induction of apoptosis inlate stage of apoptosis. Further studies are needed to further characterize the mode of action of rapamycin asan anti-cancer agent.     

蟾蜍毒素联合紫杉醇抑制人胃癌MGC803细胞增殖和诱导凋亡的作用

目的探讨蟾蜍毒素联合紫杉醇抑制人胃癌MGC803细胞增殖及诱导凋亡的作用。方法应用MTT法检测不同浓度蟾蜍毒素及紫杉醇单药及联合对胃癌细胞MGC803增殖抑制作用;流式细胞术分析细胞凋亡和周期阻滞;Westernblot法检测C-FLIPL、Caspase-8蛋白的表达。结果(1)蟾蜍毒素及紫杉醇单药均抑制MGC803细胞增殖,呈剂量-时间依赖效应,且联合用药的细胞增殖抑制率明显高于单药组,差异有统计学意义(P<0.05)。24、48及72 h联合指数(CI)分别为0.77、0.86、0.72;(2) 40 nmol/L蟾蜍毒素、25 ng/ml紫杉醇单药及联合作用细胞24 h,流式细胞仪检测凋亡率分别为14.13%、19.74%及53.30%,联合组与单药组比较差异有统计学意义(P<0.05);(3)Western blot结果显示,蟾蜍毒素、紫杉醇单药组及联合组作用细胞24 h后,C-FLIPL蛋白表达依次下降至对照组的78.38%、64.71%、46.73%,Caspase-8蛋白表达上调至对照组的150.25%,156.86%,180.58%。结论蟾蜍毒素协同紫杉醇诱导胃癌MGC803细胞凋亡,且可能与下调C-FLIP、上调Caspase-8蛋白有关。     

Toremifene诱导MCF-7/ADR细胞凋亡的研究

目的研究Toremifene体外诱导乳腺癌耐药细胞MCF-7/ADR凋亡和凋亡相关基因Fas、FasL、p53和Caspase-3表达的关系.方法以不同浓度Toremifene(0.24μg/ml、2.4μg/ml、24μg/ml)诱导MCF-7/ADR细胞凋亡;以MTT法观察不同处理浓度的Toremifene对MCF-7/ADR细胞DNA合成活性的影响;以免疫组化检测Fas、FasL、p53和Caspase-3蛋白表达.结果不同浓度Toremifene处理的MCF-7/ADR细胞出现DNA合成活性下降,抑制强度与浓度有关(P＜0.05);Fas、FasL、p53和Caspase-3蛋白呈上调表达.结论Toremifene能诱导细胞凋亡;增加Fas、FasL、p53和Caspase-3基因表达;并且与启动Caspase-3凋亡信号和p53直接介导的凋亡有关.