TRAIL受体在肿瘤细胞系上的表达及意义

目的 检测TNF相关凋亡诱导配体（TRAIL）的受体，在来源于血液系统、肝脏、肺脏和大肠的8个肿瘤细胞系中的表达，并探讨其意义。方法 采用半定量RT－PCR，对TRAIL受体的表达进行半定量检测。结果 TRAIL凋亡通路中，能够诱导凋亡反应的死亡受体DR4和DR5，在所检测的肿瘤细胞系中都有表达，其中DR5在所有肿瘤细胞系中的表达水平均显著高于DR4（P＜0．05）。而能够竞争性与TRAIL诱导的凋亡反应的诱骗受体DcR1和DcR2，在所有的肿瘤细胞中都呈低水平表达或不表达。结论 DR5可能在TRAIL诱导凋亡的通路中发挥最重要的作用。TRAIL死亡受体和诱骗受体在肿瘤细胞系中的表达具有差异性，这种差异性可在一定程度上解释不同细胞对TRAIL诱导凋亡的敏感度。     

慢性乙肝患者外周血单个核细胞TRAIL受体表达及其临床意义

目的探索慢性乙肝患者外周血单个核细胞(PBMC)肿瘤细胞坏死因子相关的凋亡诱导配体(TRAIL)受体在PBMC凋亡中的作用,及其与机体肝脏损伤的相关性。方法用RT-PCR和流式细胞术检测55例慢性乙肝患者(包括轻度、中度、重度)外周血单个核细胞TRAIL各受体(DR4、DR5、DcR1和DcR2)表达水平,同时检测肝功能相关指标,并进行相关性分析。以30例正常人作为对照。结果诱骗受体DcR1在慢性乙肝患者中的表达显著低于对照组(P<0.05)。DcR1的表达随慢性乙肝病情的加重而逐渐降低。慢性乙肝患者的DcR1表达与转氨酶(ALT)呈显著负相关,与血清白蛋白成显著正相关。结论慢性乙肝患者外周血单个核细胞DcR1表达下调可能是其细胞凋亡增加的机制之一,且DcR1表达情况可从一定程度上反映肝脏的损伤程度。     

重组人可溶性TRAIL分子诱导白血病细胞株凋亡的研究

比较重组人可溶性TRAIL(rhsTRAIL)诱导Jurkat细胞株、K562细胞株以及HL-60细胞株凋亡之间的差异,探讨这些差异与细胞表面TRAIL受体(DR4、DR5、DcR1和DcR2)表达量的关系。不同浓度的rhsTRAIL分别处理Jurkat细胞、K562细胞和HL-60细胞12 h、24 h和48 h后,用流式细胞仪检测经碘化丙啶(PI)染色后的细胞凋亡情况;用RT-PCR方法检测细胞表面受体DR4、DR5、DcR1、DcR2的表达。培养12 h、24 h、48 h后,不同浓度rhsTRAIL诱导Jurkat细胞株的凋亡率均明显高于对照组,且具有剂量依赖性和时间依赖性;但K562细胞株和HL-60细胞株未见明显的凋亡发生。RT-PCR结果显示,培养12 h、24 h、48 h后,Jurkat细胞株表面DR4的表达随时间的延长和rhsTRAIL浓度的升高而升高,而DR5、DcR1和DcR2的表达未检出;K562和HL-60细胞株表面DR4的表达没有明显变化,而且DR5、DcR1和DcR2的表达也未检出。rhsTRAIL诱导Jurkat细胞株的凋亡具有剂量依赖性和时间依赖性,且与其细胞表面DR4的表达呈正相关;在一定的浓度条件下,rhsTRAIL未能诱导K 562和HL-60细胞株发生明显凋亡,且其细胞表面DR4的表达也未见明显变化。这些结果提示,应用TRAIL治疗不同种类白血病时,应注意它的使用剂量和适应范围。     

肿瘤坏死因子相关凋亡诱导配体在多种疾病中的生物学作用

肿瘤坏死因子相关凋亡诱导配体（Apo2L/TRAIL）是肿瘤坏死因子家族的一员,可以诱导表达特异性死亡受体TRAIL-R1 （DR4）或TRAIL-R2 （DR5）的细胞凋亡.TRAIL可诱导多种肿瘤细胞凋亡,对正常细胞无杀伤性,因此将其作为抗肿瘤靶向治疗候选药物之一,备受关注.近期研究发现,TRAIL既通过其受体介导细胞凋亡信号通路,又可传导非凋亡的信号通路,在自身免疫病和感染性疾病中发挥重要生物学作用.因而简单阐明TRAIL在人类多种疾病中生物学作用的研究进展,对今后TRAIL研究方向和治疗策略的选择具有指导意义.     

膜结合配体依赖的TRAIL抗肿瘤细胞旁观者效应

目的：研究TRAIL基因抗肿瘤作用旁观者效应的发生机制。方法：腺病毒Ad/Lac-Z转染肿瘤细胞后作为标记的旁观者细胞，腺病毒Ad/g-TRAIL 转染肿瘤细胞作为效应细胞，在6孔Transwell培养板上同一孔内应用隔离或混合培养旁观者细胞和效应细胞的方法，通过检测旁观者细胞Lac-Z酶的活性，以明确TRAIL基因旁观者效应的发生机制。结果：检测了不同来源的肿瘤细胞株，包括大肠癌细胞株DLD1和Lovo、肺癌细胞株A549、肝癌细胞株HepG2、乳腺癌细胞株MDA-MB231、卵巢癌细胞株DOV13。各株肿瘤细胞转染Ad/g-TRAIL后ELISA方法均未检测出培养液中出现可溶性TRAIL（s-TRAIL）；隔离培养效应细胞与旁观者细胞，旁观者细胞的Lac-Z活性与PBS及腺病毒Ad/CMV-GFP对照组无明显差异，而混合培养组其活性明显低于对照组（P<0.05）；混合培养效应细胞与旁观者细胞（1∶1），发现高密度细胞生长组其旁观者效应明显大于低密度生长组（P<0.05 ）；FACS检测Sub G0/G1 发现DOV13细胞在高密度生长组显著高于低密度生长组（P<0.05）；荧光及相差显微镜下观察发现TRAIL转染细胞可诱导周围旁观者细胞发生凋亡而自己并不首先发生凋亡。结论：腺病毒介导的TRAIL基因的旁观者效应是通过TRIAL蛋白表达并定位于细胞膜上，通过细胞接触结合于邻近肿瘤细胞膜上的TRAIL受体而诱导旁观者肿瘤细胞的凋亡，而不是通过水解膜配体形成s-TRAIL而发生旁观者效应，这种作用是细胞接触依赖的。     

TRAIL联合紫杉醇诱导胃腺癌SGC-7901细胞凋亡作用研究

目的:观察紫杉醇联合肿瘤坏死因子相关凋亡诱导配体(TRAIL)诱导人胃腺癌SGC-7901细胞凋亡的作用及其协同作用机制。方法:将TRAIL、紫杉醇及TRAIL联合紫杉醇诱导SGC-7901细胞48小时,用流式细胞仪(FCM)检测细胞凋亡率和线粒体跨膜电位的改变;用MTT法检测SGC-7901细胞增殖反应;用免疫印迹(Westernblot)法检测TRAIL死亡受体DR4(TRAIL-R1)、DR5(TRAIL-R2)的表达变化。结果:TRAIL和/或紫杉醇对SGC-7901细胞增殖有抑制作用,两者联合用药组对细胞增殖的抑制率较单独用药明显增加(P<0.01);联合用药组细胞凋亡率较单独用药组明显增加(P<0.01);0.3μmol/L紫杉醇作用48小时后,DR4表达明显升高(P<0.05),而DR5表达没有明显改变(P>0.05)。结论:紫杉醇可协同TRAIL诱导SGC-7901细胞凋亡,DR4表达增加可能是其协同作用的机制。     

绒毛中TRAIL及其受体的表达与不明原因反复自然流产的相关性的探讨

目的探讨肿瘤坏死因子相关凋亡诱导配体TRAIL及其受体在不明原因早期反复自然流产患者(URSA)绒毛中的表达及二者的相关性。方法选择实验组妊娠45～60 d的URSA患者15例,对照组健康人工流产15例。两组分别取绒毛组织采用免疫组化法检测TRAIL及其受体的表达,进行方差分析和t检验比较两组绒毛组织中TRAIL及其受体蛋白表达水平的差异。结果实验组绒毛组织中TRAIL及其受体DR4、DR5蛋白表达较强,而诱骗受体DcR1及DcR2蛋白与正常对照相比表达较少,P值均小于0.05。结论TRAIL及其受体可能是造成自然流产的机制之一。     

DcR3重组蛋白对糖尿病大鼠心肌组织凋亡相关分子的表达及细胞凋亡的作用

目的:研究诱骗受体3(DcR3)在正常大鼠、糖尿病(DM)大鼠心肌组织的表达,DcR3重组蛋白对心肌组织凋亡相关分子表达以及心肌细胞凋亡的影响,探讨DcR3对DM大鼠心肌细胞凋亡的作用。方法:一次性腹腔注射链脲佐菌素建立大鼠DM模型,尾静脉注射不同剂量的DcR3重组蛋白[1.2 mg/(鼠·d)、0.8 mg/(鼠·d)、0.4 mg/(鼠·d)]40 d。RTPCR检测心肌组织DcR3 mRNA、Fas mRNA、FasL mRNA的表达。Wester blot分析凋亡相关蛋白Bcl-2、Caspase-8的表达。双抗夹心ELISA检测血液中IL-1β、TNF-α及LFN-γ水平的变化,HE染色观察心肌细胞凋亡的百分率。结果:DcR3治疗组大鼠与DM组比较心肌组织DcR3 mRNA高表达,Fas mRNA、FasL mRNA表达下调。Caspase-8蛋白水平下调,Bcl-2蛋白水平上调,以中剂量组的作用最明显。各DcR3治疗组血清IL-1β、TNF-α和IFN-γ水平均有不同程度的降低(P<0.05,P<0.01)。心肌细胞凋亡的百分率下降(P<0.05)。结论:DcR3重组蛋白有抑制DM大鼠心肌细胞凋亡的作用,其机制与竞争Fas,阻断FasL诱导细胞凋亡,心肌细胞表达DcR3,凋亡相关因子Caspase-8下调、Bcl-2上调及细胞因子水平的降低有关。     

IFN-γ对TRAIL诱导HBV相关性肝癌细胞凋亡的调节作用

目的：以转染了HBV全基因组、并稳定表达HBV病毒颗粒的HepG2.2.15细胞为细胞模型，探讨IFN-γ对新型凋亡分子TRAIL（TNF相关的诱导凋亡配体）诱导凋亡的影响，并初步探索其发生机制。方法：以流式细胞仪检测IFN-γ和TRAIL作用前，HepG2.2.15细胞的凋亡率，分别用流式细胞术和半定量RT－PCR的方法检测IFN-γ用0、6、12和24h后，细胞表面膜结合型TRAIL和TRAIL受体mRNA的表达。用HBsAg和HBeAg ELISA检测试剂盒测定IFN-γ作用0、6、12和24h后，HBV病毒颗粒的分泌表达状况。结果：TRAIL单独作用、IFN-γ单独作用、TRAIL和IFN-γ联合作用后，HepG2.2.15细胞的凋亡率分别为9．12％、5．84％和46．68％，表明IFN-γ可以显著上调TRAIL诱导的细胞凋亡。IFN-γ作用后，细胞表面膜型TRAIL的表达有显著上调，而部分与TRAIL诱导凋亡相关的TRAIL受体的表达也有不同程度的上调，并且IFN-γ可以抑制HepG2.2.15细胞HBV病毒颗粒的分泌。结论：转染HBV全基因组的HepG2.2.15细胞对TRAIL诱导的凋亡相对耐受,而IFN-γ却可以逆转这种耐受，使其变得对TRAIL诱导的凋亡敏感，其发生机制可能是通过IFN-γ上调细胞表面TRAIL及其受体的表达，以及抑制HBV病毒颗粒的分泌实现的。     

TNF相关的凋亡诱导配体及其受体研究进展

TNF相关的凋亡诱导配体 (TNF- related apoptosis- induicing ligand,TRAIL ) ,属于 TNF超家族成员 ,与 Apo- 1 L (Fas L )有较高的同源性 ,又称为 Apo- 2 L。 TRAIL有两类受体 ,一类是死亡受体 ,如 DR4和 DR5 ,TRAIL与 DR4或 DR5结合可以诱导细胞凋亡 ;另一类是“诱骗”受体 ,如 Dc R1、Dc R2 ,可以竞争性地与 TRAIL结合 ,逃避或抑制 TRAIL诱导的正常细胞损伤。 TRAIL及其受体的发现为肿瘤的治疗提供了一个新的方向。     

Expression of TRAIL (TNF-related apoptosis-inducing ligand) and its receptors in normal colonic mucosa,adenomas, and carcinomas

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in tumour cell lines. Four membrane-bound receptors for TRAIL have been identified, two apoptosis-mediating receptors, DR4 and DR5, and two apoptosis-inhibiting receptors, DcR1 and DcR2. The aim of this study was to examine the role of TRAIL and its receptors in colorectal cancer development. The immunohistochemical expression and localization of TRAIL and its receptors were investigated in normal mucosa (n=10), adenomas (n=19), and carcinomas (n=21). Correlations between the expression of TRAIL and its receptors and the degree of apoptosis (assessed by M30 expression) and histopathological characteristics were explored. TRAIL and its receptors were expressed in normal mucosal epithelium. Expression of the receptors was seen in adenomas and carcinomas. TRAIL expression was lost in a subset of colorectal tumours, more frequently in carcinomas than in adenomas (p<0.05). DR4 and DR5 staining was stronger in neoplastic cells than in normal cells and was accompanied by a higher degree of apoptosis. No differences were found between tumour and normal cells regarding DcR1 and DcR2 expression. No correlations were found between TRAIL or TRAIL receptor expression and histopathological characteristics. In conclusion, marked changes were seen in the course of the adenoma-carcinoma sequence with respect to the expression of TRAIL and TRAIL receptors DR4 and DR5. The stronger expression of DR4 and DR5 in neoplastic cells than in normal cells, together with a higher degree of apoptosis, suggests a possible functional role for these receptors in apoptosis induction in neoplastic colorectal cells.     

Characterization of tumour necrosis factor-alpha-related apoptosis-inducing ligand and its receptors in the adult human testis

Tumour necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) is a member of the tumour necrosis factor-alpha (TNF-alpha) family of cytokines which is known to induce apoptosis upon binding to its death domain-containing receptors, DR4/TRAIL-R1 and DR5/TRAIL-R2. Two additional TRAIL receptors, DcR1/TRAIL-R3 and DcR2/TRAIL-R4, lack functional death domains and act as decoy receptors for TRAIL. In this study, the presence of TRAIL and its receptors was investigated by immunohistochemistry in adult human testes. In addition, TRAIL and its receptors were studied in terms of protein and mRNA using western blot analysis and RT-PCR respectively. TRAIL and its receptors were immunodetected according to the different testicular cell types: TRAIL, DR5/TRAIL-R2 and DcR2/TRAIL-R4 were localized in Leydig cells, DR4/TRAIL-R1 was seen in peritubular and Sertoli cells whereas ligand and all receptors were detected in germ cells. Proteins and mRNA corresponding to TRAIL and its receptors were also identified in adult human testes. In conclusion, TRAIL and its receptors DR4/TRAIL-R1, DR5/TRAIL-R2, DcR1/TRAIL-R3 and DcR2/TRAIL-R4 are expressed in the human testis, and are predominantly localized in different germ cell types.     

Progression in melanoma is associated with decreased expression of death receptors for tumor necrosis factor-related apoptosis-inducing ligand

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in melanoma by interaction with death receptors TRAIL-R1 (DR4) or TRAIL-R2 (DR5) on melanoma cells or resists apoptosis by interaction with decoy receptors TRAIL-R3 (DcR1) or TRAIL-R4 (DcR2). Studies on cell lines suggest that there is a wide variation in TRAIL death receptor expression; however, their expression on excised human melanoma is not well documented. In view of this, we studied death receptor expression on melanomas using monoclonal antibodies specific for these receptors. Immunohistochemical staining for DR4, DR5, and DcR1/DcR2 was performed on formalin-fixed paraffin-embedded sections of 100 cases of primary melanoma, metastatic melanoma, and benign nevi. Percentage expressions of DR4 versus DR5 in benign nevi, primary melanoma, and melanoma metastases were 40% versus 90%, 69% versus 98%, and 55% versus 66%, respectively. There were significant differences in the mean percentage of DR5-positive cells between different groups of melanocytic lesions. Percent expression was higher in thin (< or =1.0 mm) compared with thick primary melanoma (88.9% versus 66.9%), and expression was less in subcutaneous metastases (49%) and lymph node metastases (30.6%) (P < .005). Expression was also higher in compound nevi (57%) than dysplastic nevi (49%). DcR1/DcR2 was found in 75% of benign nevi, 62% of primary melanomas, and 74% melanoma metastases. The results showed a wide variation in the expression of death receptors for TRAIL between and within primary and metastatic melanoma and a decreased expression on the thick primary melanoma and metastatic melanoma. This suggests that melanoma may not respond to treatment with TRAIL unless given with agents that increase the expression of TRAIL death receptors.     

Application of flow cytometry to molecular medicine: detection of tumor necrosis factor-related apoptosis-inducing ligand receptors in acute myeloid leukaemia blasts

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), a cytokine belonging to the TNF (tumor necrosis factor) family, is currently regarded as a potential anti-cancer agent. Nevertheless, several types of cancer cells display a low sensitivity to TRAIL or are completely resistant to this pro-apoptotic cytokine. TRAIL signalling is dependent on four receptors. Two of them, death receptors 4 and 5 (DR4 and DR5), induce apoptosis, whereas decoy receptors 1 and 2 (DcR1 and DcR2) are unable to evoke cell death upon TRAIL binding. TRAIL resistance may be related to the expression of TRAIL decoy receptors. TRAIL has been proposed as a novel therapeutic agent for the treatment of haematological disorders, including acute myeloid leukaemia (AML). Surprisingly, however, very limited information is available concerning the expression of TRAIL receptors in AML blasts. Here, we have evaluated, using flow cytometry, TRAIL receptor surface expression and sensitivity to TRAIL-dependent apoptosis of AML blasts from 30 patients. We observed frequent expression of TRAIL DcR1 and DcR2, while expression of DR4 and DR5 was less frequent. Nevertheless, the expression of DR4 or DR5 in leukaemic cells was always matched by a similar expression of one of the decoy receptors. Leukaemic blasts were invariably resistant, even to a high concentration (1000 ng/ml) of TRAIL. We suggest that AML blasts are resistant to TRAIL apoptosis in vitro. Therefore, it is unlikely that TRAIL alone might be used in the future as an innovative pharmacological agent for the treatment of AML.     

Osteoprotegerin (OPG) acts as an endogenous decoy receptor in tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis of fibroblast-like synovial cells

We examined the role of osteoprotegerin (OPG) on tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in rheumatoid fibroblast-like synovial cells (FLS). OPG protein concentrations in synovial fluid from patients with rheumatoid arthritis (RA) correlated with those of interleukin (IL)-1beta or IL-6. A similar correlation was present between IL-1beta and IL-6 concentrations. Rheumatoid FLS in vitro expressed both death domain-containing receptors [death receptor 4 (DR4) and DR5] and decoy receptors [decoy receptor 1 (DcR1) and DcR2]. DR4 expression on FLS was weak compared with the expression of DR5, DcR1 and DcR2. Recombinant TRAIL (rTRAIL) rapidly induced apoptosis of FLS. DR5 as well as DR4 were functional with regard to TRAIL-mediated apoptosis induction in FLS; however, DR5 appeared be more efficient than DR4. In addition to soluble DR5 (sDR5) and sDR4, OPG administration significantly inhibited TRAIL-induced apoptogenic activity. OPG was identified in the culture supernatants of FLS, and its concentration increased significantly by the addition of IL-1beta in a time-dependent manner. Neither IL-6 nor tumour necrosis factor (TNF)-alpha increased the production of OPG from FLS. TRAIL-induced apoptogenic activity towards FLS was reduced when rTRAIL was added without exchanging the culture media, and this was particularly noticeable in the IL-1beta-stimulated FLS culture; however, the sensitivity of FLS to TRAIL-induced apoptosis itself was not changed by IL-1beta. Interestingly, neutralization of endogenous OPG by adding anti-OPG monoclonal antibody (MoAb) to FLS culture restored TRAIL-mediated apoptosis. Our data demonstrate that OPG is an endogenous decoy receptor for TRAIL-induced apoptosis of FLS. In addition, IL-1beta seems to promote the growth of rheumatoid synovial tissues through stimulation of OPG production, which interferes with TRAIL death signals in a competitive manner.     

TRAIL与顺铂协同诱导横纹肌肉瘤细胞凋亡时Fas和cFLIP表达的改变及其意义

目的:探讨肿瘤坏死因子相关凋亡诱导配体(TRAIL)及其基因Ad／GT-TRAIL和顺铂(DDP)联合应用对人横纹肌肉瘤细胞生长抑制和诱导凋亡作用,并分析细胞表面Fas蛋白和细胞内cFLIPmRNA表达对凋亡的影响。方法:将TRAIL(100μg/L)、Ad／GT-TRAIL和顺铂作用于培养的人RD横纹肌肉瘤细胞,通过MTT比色法、流式细胞仪检测细胞凋亡和Fas蛋白表达、RT-PCR检测cFLIPmRNA表达,观察和分析TRAIL及其基因Ad／GT-TRAIL对横纹肌肉瘤细胞的作用及和顺铂协同作用的机制。结果:Ad／GT-TRAIL和100μg/LTRAIL对横纹肌肉瘤细胞的生长抑制率分别为52.5%和43.5%,凋亡诱导率为12.95%和10.26%,联合应用顺铂,生长抑制率和凋亡诱导率均显著高于单独应用(P<0.05),FCM分析显示联合应用提高了Fas蛋白的表达,RT-PCR显示cFLIPmRNA表达下降,与联合应用组细胞凋亡率增加相一致。结论:TRAIL和Ad／GT-TRAIL能有效诱导横纹肌肉瘤细胞的凋亡从而抑制横纹肌肉瘤细胞的生长,联合应用顺铂可显著提高疗效。     

TRAIL及其受体DR5与动脉粥样硬化关系的初步研究

目的探讨肿瘤坏死因子(INF)相关的凋亡诱导配体(TRAIL)及其受体DR5与动脉粥样硬化(AS)之间的关系。方法冠心病(CAD)组61例,正常对照组22例。应用酶联免疫吸附法测定血浆可溶性TRAIL(sTRAIL)和可溶性DR5(sDR5)水平。免疫组织化学测定冠状动脉TRAIL和DR5蛋白表达情况。结果CAD组血浆sTRAIL和sDR5水平均显著性升高(P<0.001,P<0.05)。3支血管病变组和双支血管病变组血浆sTRAIL和sDR5水平均分别显著高于单支血管病变组和正常对照组(P<0.01,P<0.01,P<0.01,P<0.05)。TRAIL和DR5主要表达于平滑肌细胞的胞质,TRAIL还可表达于AS中的巨噬细胞。AS组冠状动脉的TRAIL和DR5表达明显高于非AS组(P<0.01,P<0.05)。结论TRAIL及其受体DR5可能参与了AS的进展,其浓度越高,冠状动脉病变越重。     

白花丹醌增强TRAIL诱导Kasumi-1细胞凋亡及其机制

目的: 观察白花丹醌、rsTRAIL单独及其联合体外诱导Kasumi-1细胞凋亡的作用,探讨其作用机制。方法: 采用WST-8 (CCK-8)比色法测定rsTRAIL、白花丹醌单独和联合应用对Kasumi-1细胞的生长抑制率;用流式细胞术、TUNEL法观察并且检测凋亡率;实时定量PCR检测白花丹醌作用后DR4和DR5 mRNA水平变化;Western blotting法检测单独应用及联合应用后DR5、caspase-3、caspase-8、caspase-9、Bid、Bax及c-FLIP的变化。结果: (1)白花丹醌和rsTRAIL单独应用均可抑制Kasumi-1细胞的生长,联合应用可增加对Kasumi-1细胞的生长抑制率且呈时间和剂量依赖性(P<0.05)。(2)rsTRAIL(100 μg/L)和白花丹醌(2 μmol/L)单用及其联合使用诱导Kasumi-1细胞Annexin V阳性细胞百分率分别为(27.7±2.9)%、(25.6±3.1)%和(52.1±3.3)%。(3)TUNEL法检测发现联合应用组较单用组凋亡细胞显著增多。(4)实时定量PCR检测发现白花丹醌可以上调DR5的表达。(5)Western blotting发现白花丹醌单独作用及其联合rsTRAIL应用时上调DR5、激活caspase-8和下调c-FLIP表达。结论: 白花丹醌具有增强TRAIL诱导Kasumi-1细胞凋亡的作用,其机制与DR5上调、caspase-8激活和c-FLIP下调有关。