蝎毒多肽提取物对前列腺癌细胞增殖的影响

目的观察蝎毒多肽提取物（PESV）对非激素依赖性前列腺癌DU-145和PC-3细胞的生长与增殖、细胞周期及cyclinE和p27蛋白表达的影响。方法采用噻唑蓝（MTT）法检测PESV对前列腺癌细胞PC-3和DU—145生长与增殖的影响，流式细胞术观察药物对细胞周期的影响，免疫组织化学法检测药物干预后，cyclinE和p27蛋白水平表达的变化。结果MTT显示，PBSV在浓度40-200μg／ml时对前列腺癌细胞毒性作用明显（40μg／ml时，DU—145细胞抑制率为30．5％，PC-3细胞抑制率为33．1％，与阴性对照组相比，P〈0．05），且随剂量加大作用增大，浓度在200μg／ml时，100％抑制，呈明显剂量效应关系；流式细胞术显示，PESV干预后G0／G1细胞的百分比增多，S期的前列腺癌细胞减少（DU-145细胞和PC-3细胞S期的比例分别为34．1％和17．1％，与阴性组比较，P〈0．01）；免疫组化显示，PBMV干预后，DU-145和PC-3细胞cyclinE蛋白表达水平下调，p27蛋白表达水平上调。结论PESV对前列腺癌细胞增殖具有抑制作用。对前列腺癌治疗具有潜在价值。     

蝎毒多肽提取物诱导前列腺癌DU-145细胞凋亡的实验研究

目的探讨蝎毒多肽提取物（PESV）诱导前列腺癌DU-145细胞凋亡的作用及机制。方法用PEsV（40μg／mL）处理DU-145细胞，采用Gimeea染色法观察凋亡细胞形态变化；采用免疫组化S-P法检测核增殖抗原Ki-67及凋亡相关基因bax和bcl-2的表达，并用病理图像分析软件进行半定量分析；TUNEL法检测凋亡细胞，并计算前列腺癌细胞增殖指数（proliferating index，PI）和凋亡指数（apoptosis index，AI）。结果PESV在体外对DU-145细胞有中度增殖抑制效应；在PESV作用下，DU-145细胞出现显著的细胞凋亡征象，凋亡指数明显增高，增殖指数降低．AI／PI明显增高（P〈0．05）。PESV处理DU-145细胞可明显提高凋亡相关基因bax表达水平，降低凋亡抑制蛋白Bcl-2表达水平，使Bel-2／Bax比值明显减小（P〈0．05）。结论PESV（40μg／mL）可以诱导细胞凋亡，而且至少是通过促进Bax、抑制Bel-2基因表达的机制诱导细胞凋亡。     

蝎毒注射液治疗癌痛

目的：观察施康宁注射液（内含蝎毒蛋白）对癌痛的镇痛作用。方法：本次临床试验分对照试验（共41例,以随机双盲的原则分为两组： 施康宁组21例、安慰剂组20例）和开放试验（共88例,均用施康宁注射液,用药7天67例,用药14天21例）两部分。结果：在对照试验中,施康宁组疼痛强度差和总疼痛强度差高于安慰剂组,（P＜0．05－0．01）;施康宁组2－4小时中度以上缓解率均为52．4％,明显优于安慰剂组,P＜0．05,有显著性差异。施康宁组总有效率为80．95％,安慰剂组为45％,P＜0．05,有显著性差异,开放试验中,7天用药组和14天用药组的中度以上缓解率分别为71．6％和95．2％,两组用药后各时段能强度均降低,与用药前相比,P均＜0．001。用蝎毒注射液后1－4小时镇痛效果最佳,用药后总疼痛强度差（SPID）逐天提高,无明显的过敏反应,副反应小。结论：说明施康宁注射液（蝎毒蛋白）对癌痛有镇作用、镇痛效果以用药后1－4小时为最佳,且随着用药天数的延长而镇痛效果增加,不良反应较少,无成瘾性,可作为轻、中度部患者的理想镇痛药物。     

姜黄素诱导人膀胱癌UMUC2细胞株凋亡的作用

目的为寻找有效无毒的膀胱灌注药物用于膀胱肿瘤术后预防肿瘤种植与复发,我们观察了姜黄素对人膀胱癌细胞UMUC2的细胞毒效应及诱导凋亡的体外作用。方法以0~160 μmol/L姜黄素作用于UMUC2细胞1~48 h,应用MTT法、平板克隆实验观察姜黄素的细胞毒效应,荧光染色观察凋亡形态学改变,流式细胞仪进行细胞周期分析及凋亡定量测定,免疫细胞化学染色观察凋亡相关蛋白p53和Survivin的表达。结果所有浓度组姜黄素均对膀胱癌UMUC2细胞有明显的生长抑制作用,160 μmol/L姜黄素作用1 h对全部癌细胞是致命的。荧光染色观察到典型的核凝集、碎裂凋亡形态学改变。流式细胞术定量分析了亚G1峰,后者同时表明姜黄素导致的细胞周期阻滞以G2/M期为主,使S期细胞比例显著减少。免疫细胞化学染色显示姜黄素下调p53、Survivin蛋白的表达。结论姜黄素明显抑制膀胱癌细胞系UMUC2的生长并诱导凋亡,导致细胞G2/M期阻滞,其作用机制与其下调p53、Survivin的表达相关,克隆形成实验证实大剂量姜黄素、短期作用对膀胱癌细胞系UMUC2有致命的细胞毒效应,显示了姜黄素用于膀胱癌患者的化学治疗,尤其是腔内灌注化疗的可能性。     

Apoptosis of Colorectal Cancer UTC116 Cells Induced by Cantharidinate

Effects of Cantharidinate on apoptosis of human colorectal cancer UTC-116 cells were investigated by meansof 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, H and E staining, flow cytometry,and Raman Spectra analysis. The results showed Cantharidinate to exert inhibitory action on proliferationof human colorectal cancer UTC-116 cells, inducing apoptosis, arresting cells in G1 phase, with decline of Sand G2 phases. In addition, the results of Raman spectrum showed significant changes in the UTC-116 cellschemical structure with stretching after the application of Cantharidinate. Taken together, these results suggestthat the treatment of human colorectal cancer with Cantharidinate may be associated with multiple molecularmechanisms for apoptosis. Furthermore, similar to fluorouracil, Cantharidinate should be considered as novelassistant drug for controlling the growth of human colorectal cancer UTC-116 cells.     

pVITRO2-VSVM-MBD2抑制肺癌细胞增殖并诱导其凋亡的实验CSCD

目的探讨β防御素-2(MBD2)与水泡口炎病毒基质蛋白双表达质粒对肺癌细胞增殖的影响及其体外对DC细胞的趋化作用。方法MTT法观察各组质粒转染后肺癌LL/2细胞的增殖抑制率,PI荧光染色观察细胞形态变化,Annexin V-PE/7-AAD双染法检测细胞凋亡情况。树突状细胞(DC)趋化实验观察各质粒转染组LL/2细胞上清液中MBD2的活性。结果pVSVM(Lipofectamine 2000转染细胞后转入pVSVM)、pVSVM+pMBD2共转染组和pVSVM-MBD2双表达质粒转染组(M蛋白会在肿瘤细胞内同时表达)细胞形态变化明显,与脂质体转染组(Lipofectamine 2000转染细胞)相比明显抑制了LL/2细胞的增殖。空白对照组(不转染Lipofectamine 2000)和pMBD2转染组(Lipofectamine 2000转染细胞后转入pMBD2)细胞凋亡率较低,而其他转染组细胞凋亡率明显增加,且双表达质粒具有更强的凋亡诱导作用。pMBD2具有良好的DC趋化作用。结论β防御素-2与水泡口炎病毒基质蛋白共表达质粒能显著抑制肺癌细胞LL/2的增殖并诱导其凋亡,且有体外趋化DC细胞活性的能力。     

蝎毒多肽提取物对白血病细胞株K562/A02荷瘤鼠耐药性的影响

目的 探讨蝎毒多肽（peptide extract from scorpion venom,PESV）逆转白血病干细胞（leukemiastem cells, LSC）在体内多药耐药（multidrug resistance, MDR）的分子机制。方法 以多药耐药的K562/A02细胞株成模白血病BALB/c裸鼠为例,成模鼠随机分为6组：模型对照组、阿霉素（ADM）组、PESV组、ADM+PESV（H）组、ADM+PESV（M）组、ADM+PESV（L）组。模型对照组给予等体积0.9%氯化钠溶液腹腔注射,其余各组予相应剂量ADM和（或）PESV腹腔注射,连续给药14天。第21天观察各组裸鼠移植瘤生长情况,分别检测瘤块中LSC：细胞膜上P-gp的表达,细胞质中ALDH、PI3K的变化及细胞核中MDR1、NF-κB的活性。结果 K562/A02细胞经免疫磁珠分选前后的CD34+CD38-细胞比率和IC50值分别为31.5%、（60.33±10.68）μg/ml和92.8%、（58.33±9.72）μg/ml,分选后细胞干性显著提高,而耐药性无差异性损失;各组造模裸鼠成瘤率100%。瘤体中LSC：流式细胞仪检测细胞膜上P-gp表达结果：检测对照组89.8%、ADM组91.9%、PESV组88.4%、ADM+PESV（H）组53.9%、ADM+PESV（M）组78.0%、ADM+PESV（L）组78.7%;半定量RT-PCR检测MDR1 mRNA的表达：PESV组＞ADM+PESV（L）组＞ADM+PESV（M）组＞ADM+PESV（H）组＞ADM组;免疫组织化学检测ALDH,显示灰度值ADM组＞PESV组＞ADM+PESV（H）组＞ADM+PESV（M）组＞ADM+PESV（L）组;Western blot检测PI3K分子与Elisa检测NF-κB因子结果一致,在ADM组、PESV组表达上调,在ADM+PESV组中表达下调,下调强度与PESV剂量呈正相关。结论 PESV具有下调白血病干细胞膜上P-gp,细胞质内ALDH、PI3K及细胞核中MDR1、NF-κB的表达水平,增强了白血病K562/A02干细胞在体内对ADM的敏感度,逆转其多药耐药特性。     

Participation of Omi Htra2 Serine-Protease Activity in the Apoptosis Induced by Cisplatin on SW480 Colon Cancer Cells

Abstract

Apoptosis is triggered by two interconnected pathways, extrinsic and intrinsic. The intrinsic pathway is activated by genomic stress promoting mitochondrial release of apoptotic proteins. One of these proteins is Omi/Htra2, a serine protease which inactivates Inhibitor of Apoptosis Proteins (IAPs). In the present work, we assessed the participation of Omi/Htra2 in the cell death induced by the chemotherapeutic drugs 5-fluorouracil (5-FU) and cisplatin (CDDP) in SW480 colon cancer cells. CDDP and 5-FU induced apoptosis mediated by the intrinsic pathway in colon cancer cells, as demonstrated by morphological analyses, mitochondrial cytochrome c release and cleavage of caspase 3. Omi/Htra2 was also released from mitochondria of cells exposed to these drugs, as demonstrated by immunofluorescence and western blot assays of subcellular fractions. Exposure of cells to the Omi/Htra2 serine protease inhibitor UCF-101 prevented death p<0.0001 and partially suppressed reproductive cell death of cells exposed to cisplatin p<0.05, but not to 5-FU p=0.49. From these experiments we show that Omi/Htra2 serine protease activity participates in the cell death induced by CDDP but not of 5-FU in colon cancer cells.     

Menadione (Vitamin K3) Induces Apoptosis of Human Oral Cancer Cells and Reduces their Metastatic Potential by Modulating the Expression of Epithelial to Mesenchymal Transition Markers and Inhibiting Migration

Oral cancer is one of the most commonly occurring cancers worldwide, decreasing the patient’s survival ratedue to tumor recurrence and metastasis. Menadione (Vitamin K3) is known to exhibit cytotoxicity in variouscancer cells but the present study focused on its effects on viability, apoptosis, epithelial to mesenchymal transition(EMT), anchorage independent growth and migration of oral cancer cells. The results show that menadioneis more cytotoxic to SAS (oral squamous carcinoma) cells but not to non-tumorigenic HEK293 and HaCaTcells. Menadione treatment increased the expression of pro-apoptotic proteins, Bax and p53, with a concurrentdecrease in anti-apoptotic proteins, Bcl-2 and p65. Menadione induced the expression of E-cadherin but reducedthe expression of EMT markers, vimentin and fibronectin. Menadione also inhibited anchorage independentgrowth and migration in SAS cells. These findings reveal and confirm that menadione is a potential candidate inoral cancer therapy as it exhibits cytotoxic, antineoplastic and antimigratory effects besides effectively blockingEMT in oral cancer cells.     

口腔癌患者应用二甲双胍对KB细胞增殖及凋亡的影响

目的 研究口腔癌患者应用二甲双胍进行治疗,观察其对KB细胞的增殖以及凋亡的影响.方法 收集生化药理研究室的人口腔癌KB细胞,采用随机数字表法将人口腔癌KB细胞分别采用不同浓度的二甲双胍进行处理,并观察24 h、48 h、72 h细胞增殖的情况,采用碘化丙啶(PI)染色进行检测KB细胞的凋亡情况,采取Western blot方法分别处理不同的时间进行检测GRP78和Caspase-3蛋白的表达.结果 经过浓度为5 mol的二甲双胍进行处理的KB细胞24 h、48 h、72 h细胞存活率之间进行比较,差异具有统计学意义(P＜0.05);采用浓度分别为2.5 mol与5 mol的二甲双胍处理,细胞的凋亡率分别为12.13％、25.12％,组间比较差异均具有统计学意义(P＜0.05);采用浓度为5 mol的二甲双胍处理不同的时间,可观察到GRP78的表达被诱导且Caspase-3蛋白被激活.结论 二甲双胍作为新型的抗癌症辅助药物,具有良好的抑制人口腔癌KB细胞的增殖、并诱导其凋亡的作用,为临床治疗口腔癌提供了新的治疗途径.     

肾癌细胞凋亡的超微结构改变

目的 观察肾癌细胞凋亡的形态学特征及凋亡过程中线粒体结构的变化,揭示线粒体在细胞凋亡过程中的作用。方法 采用3种化疗药物诱导肾癌细胞发生凋亡,再于光镜和电镜下观察肾癌细胞的形态结构改变。结果 3种药物均可诱导肾癌细胞凋亡,有典型的细胞凋亡的形态学改变,线粒体结构改变早于细胞染色质结构改变。结论 线粒体在细胞凋亡的过程中起着重要的调控作用,其内部某些成分可能启动或阻止细胞凋亡的发生。     

细胞凋亡检测用于卵巢癌实体瘤体外化疗药物敏感试验

目的 评价细胞凋亡检测用于实体瘤体外化疗药物敏感试验的可行性。方法 对Ⅲｃ期原发性上皮性卵巢癌实体瘤细胞行体外分离培养,使用６种不同的抗肿瘤药物对其进行处理,经５天培养后,制成细胞涂片,末端标记法观察不同药物作用后细胞凋亡情况。结果 发现源一示同病例的卵巢癌实体瘤细胞对不同抗癌药物的敏感性存在差异,同一种抗癌药物对不同病人卵巢癌实体瘤细胞产生的凋亡程度不同。结论 细胞凋亡检测用于肿瘤的药物敏感试验     

Croton Tiglium Extract Induces Apoptosis via Bax/Bcl-2 Pathways in Human Lung Cancer A549 Cells

Objective: To investigate the impact of a Croton tiglium extract on cellular proliferation and apoptosis in a non-small cell lung cancer cell line (A549) in vitro. Methods: A Croton tiglium seed methanol extract was prepare and assessed for effects on A549 cells regarding cellular proliferation, apoptotic rates, and expression of apoptosis related genes and proteins using real-time PCR and immunofluorescence. Results: The tested Croton tiglium extract inhibited A549 cell proliferation in a dose- and time-dependent manner, with significant elevation of apoptotic indexes at various concentrations after 24 h. In addition, rates in both early and late stages were higher in treated than untreated groups, the 100 μg/ml dose causing the highest levels of apoptosis. RT-PCR showed that A549 cells treated with 100 μg/ml Croton tiglium extract for 24 h has markedly higher Bax mRNA expression levels and obviously lower Bcl-2 expression levels than controls, equivalent results being observed for proteins by immunofluorescence. However, the mRNA expression levels of Fas and caspase-8 were not significantly altered. Conclusion: A Croton tiglium extract can inhibit proliferation of A549 cells and promote apoptosis though Bax/Bcl-2 pathways.     

紫杉醇诱导人膀胱癌EJ细胞凋亡及与Bcl-2基因表达的关系

目的探讨紫杉醇对人膀胱癌EJ细胞凋亡的作用及其机制。方法体外培养人膀胱癌EJ细胞,以不同浓度紫杉醇处理12～72 h后,应用流式细胞仪检测凋亡率,测定细胞周期;原位杂交法检测紫杉醇作用后Bcl-2基因表达的变化。结果流式细胞仪检测结果发现紫杉醇诱导后的膀胱癌EJ细胞周期阻滞于G2/M期,高浓度紫杉醇（100、1 000 nmol/L）更明显,出现凋亡峰,细胞凋亡率随紫杉醇浓度的增加而增高;紫杉醇作用后Bcl-2基因表达发生明显变化,随紫杉醇浓度的增加而降低。结论紫杉醇能够诱导EJ细胞凋亡,细胞凋亡率随紫杉醇浓度的增加而增高;紫杉醇通过抑制Bcl-2基因表达而诱导细胞凋亡,为其诱导凋亡的作用机制之一。     

Naja Naja Oxiana Venom Fraction Selectively Induces ROS-Mediated Apoptosis in Human Colorectal Tumor Cells by Directly Targeting Mitochondria

Objective: To investigate the selective effect of Naja naja oxiana crude venom and its fractions on human colorectal cancer mitochondria to activate apoptosis signaling. Methods: Cells and mitochondria isolated from human cancerous and normal colorectal tissues exposed to N. oxiana crude venom and its fractions obtained from size-exclusion chromatography and then mitochondrial parameters related to up-stream cell death signalling such as reactive oxygen species formation, MMP, mitochondrial swelling, cytochrome c release and ATP content as mitochondrial parameters and activation of caspase3 and finally apoptosis/necrosis % were then assayed as cellular parameters. Result: Our findings indicated that crude venom (15, 30 and 60 μg/ml) and fraction 3; F3; (10, 20 and 40 μg/ml) of N. Oxiana venom induced a significant (p<0.05) increase of reactive oxygen species level, swelling of mitochondria, collapse of mitochondrial membrane potential (MMP), release of cytochrome c, activated caspase3 and decrease ATP content only in colon cancer tissue group but not from the healthy colon tissue group. Our results also showed that fraction 3 of venom decreased the percentage of viable cells and induced apoptosis in cancerous colorectal cells. Conclusion: F3 fraction of N. Oxiana venom is a suitable candidate for further studies as a new drug treatment of colorectal cancer due to its high capacity for induction of apoptosis signaling via mitochondrial pathway.     

Mdm2-P53 Interaction Inhibitor with Cisplatin Enhances Apoptosis in Colon and Prostate Cancer Cells In-Vitro

Objective: To study the effect of RITA (MDM2-p53 interaction inhibitor) and its action along with genotoxic drug cisplatin was evaluated on COLO-205 colon cancer and PC-3 prostate cancer cells. Method: Various in-vitro parameters to determine cytotoxic and apoptotic potential of RITA with genotoxic drug cisplatin were evaluated. The potentiation of cytotoxic effect was evaluated using MTT assay and colony forming assay, mechanism of cell death by Etbr/AcO assay and the mechanism of apoptosis was determined by caspase-3 release assay. Results: The findings from MTT confirmed the best possible potent combination of 5+5µM and 10+10µM concentration of Cisplatin and RITA respectively. These combinations were further evaluated for its chemo sensitizing effect which confirmed the significant reduction in number of colonies in combination as compared to monotherapy. Also, the results of Etbr/AcO assay were in line with the colony forming assay. For apoptotic activity, it was noted that increasing the concentration of cisplatin and RITA (10µM), did not affect much to apoptotic activity and was found to be equally effective to that of low dose (5µM) concentration. The same results were seen in Caspase-3 release effect on both the cell lines. Conclusion: Our present study provides compelling evidence that pharmacological activation of the p53 by blocking the MDM2–p53 interaction is a promising cancer therapeutic strategy and using RITA in combination with Cisplatin not only decrease the toxic effect of Cisplatin by decreasing its dose but also increasing the apoptotic effect, warrants clinical evaluation on both colon and prostate cancer.     

p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid

Oleanolic acid (OA) is a nutritional component widely distributed in various vegetables. Although it has beenwell recognized for decades that OA exerts certain anti-tumor activity by inducing mitochondria-dependentapoptosis, it is still unclear that what molecular signaling is responsible for this effect. In this study, we employedcancer cell lines, A549, BXPC-3, PANC-1 and U2OS to elucidate the molecular mechanisms underlying OA antitumoractivity. We found that activation of MAPK pathways, including p-38 MAPK, JNK and ERK, was triggeredby OA in both a dose and time-dependent fashion in all the tested cancer cells. Activation was accompaniedby cleavage of caspases and PARP as well as cytochrome C release. SB203580 (p38 MAPK inhibitor), but notSP600125 (JNK inhibitor) and U0126 (ERK inhibitor), rescued the pro-apoptotic effect of OA on A549 and BXPC-3 cells. OA induced p38 MAPK activation promoted mitochondrial translocation of Bax and Bim, and inhibitedBcl-2 function by enhancing their phosphorylation. OA can induce reactive oxygen species (ROS)-dependentASK1 activation, and this event was indispensable for p38 MAPK-dependent apoptosis in cancer cells. In vivo,p38 MAPK knockdown A549 tumors proved resistant to the growth-inhibitory effect of OA. Collectively, weelucidated that activation of ROS/ASK1/p38 MAPK pathways is responsible for the apoptosis stimulated byOA in cancer cells. Our finding can contribute to a better understanding of molecular mechanisms underlyingthe antitumor activity of nutritional components.     

Hyperin Extracted from Manchurian Rhododendron Leaf Induces Apoptosis in Human Endometrial Cancer Cells Through a Mitochondrial Pathway

Background: A number of effective prevention measures have been introduced in attempts to substantiallyreduce both the incidence and mortality due to many kinds of cancer. The search for new anti-cancer compoundsin foods or in plant medicines is one realistic and promising approach to prevention. Chinese medicines provide arich pool of novel and efficacious agents for cancer prevention and treatment. Previously it was demonstratratedthat hyperin extracted from the Manchurian rhododendron leaf reduces the proliferation of many cancer cells.The present study was carried out to evaluate its effects on human endometrial cancer cell viability and apoptosisand to investigate its mechanisms of action in RL952 cells. Methods: Cell viability was measured using the MTTassay. Intracellular calcium ions were detected using laser-scanning confocal microscopy. The effects of hyperinon apoptosis related proteins in RL952 cells were examined using Western blot analysis. Results: The growth ofRL952 cells was inhibited by treatment with hyperin. OD values of caspase-3 and caspase-9 were increased andexpression of bcl-2 was increased and bax was decreased in protein levels in RL952 cells after 24 h of hyperintreatment, Moreover, intracellular calcium accumulation occurred in hyperin-treated cells. Conclusions: Theseresults suggest that hyperin may play an important role in tumor growth suppression by inducing apoptosis inhuman endometrial cells via a Ca2+-related mitochondrion apoptotic pathway in RL952 cells.     

Effect of Embelin on TRAIL Receptor 2 mAb-induced Apoptosis of TRAIL-resistant A549 Non-small Cell Lung Cancer Cells

Introduction: Some non-small cell lung cancer (NSCLC) tumor cells are insensitive to tumor necrosis factorrelatedapoptosis-inducing ligand (TRAIL) -based therapy. This study was conducted to examine the effect ofembelin on the sensitivity of the A549 NSCLC cell line to TRAIL receptor2 (TRAILR2) monoclonal antibodiesand to investigate the potential mechanisms. Materials and Methods: A549 cells were treated with embelin,TRAILR2 mAb or a combination of both. Cell viability was measured using ATPlite assay and apoptosis rateswere determined by flow cytometry with AnnexinV-FITC and propidium iodide staining, with the expressionlevels of proteins analyzed by Western blotting. Results: The cell survival rate of separate treatments with 100ng/ml TRAILR2 antibody or 25 uM embelin were 81.5±1.57% and 61.7±2.84%, respectively. Their combined usemarkedly decreased cell viability in A549 cells to 28.1±1.97% (P<0.05). The general caspase inhibitor Z-VADFMKcould inhibit the embelin-enhanced sensitivity of A549 cells to TRAILR2 mAb (75.97±3.17%)(P<0.05).Both flow cytometry and cell morphological analysis showed that embelin was able to increase TRAIL-inducedapoptosis in A549 cells. Combined treatment with embelin and TRAILR2 mAb augmented the activation ofinitiator caspases and effector caspase. In addition, A549 cells showed increasing levels of TRAILR2 proteinand decreasing levels of Bcl-2, survivin and c-FLIP following the treatment with embelin+TRAILR2 mAb.Conclusions: Embelin could enhance TRAIL-induced apoptosis in A549 cells. The synergistic effect of thecombination treatment might be due to modulation of multiple components in the TRAIL receptor-mediatedapoptotic signaling pathway, including TRAILR2, XIAP, survivin, Bcl-2 and c-FLIP.