The action mechanism by which C1q/tumor necrosis factor-related protein-6 alleviates cerebral ischemia/reperfusion injury in diabetic mice

Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.

Antitumor effect of tumor necrosis factor-related apoptosis inducing ligand combined with mevastatin on a human glioma cell line SWO-38

BACKGROUND： Previous studies have reported that statins are less toxic to the human body and have greater antitumor activity; however, few studies have addressed the antitumor effect of statins combined with tumor necrosis factor-related apoptosis inducing ligand （TRAIL）. OBJECTIVE： To explore the effect of TRAIL combined with mevastatin on the proliferation and apoptotic cell death of a human glioma cell line SWO-38, and to study its mechanism of action. DESIGN, TIME AND SETTING： An in vitro control experiment was performed at the Central Laboratory of the Third Hospital Affiliated to Sun Yat-sen University, between January and April 2009. MATERIALS： The human SWO-38 cell line was provided by Cell Research, Department of Animal Experimental Center of Sun Yat-sen University; human recombinant soluble TRAIL by R＆D, USA; and mevastatin by Sigma, USA. METHODS： SWO-38 cells were separately incubated in TRAIL （100, 200, 300, 400, and 500 tJg/L） and mevastatin （5, 10, 20, 30, and 40 pmol/L） for 72 hours. In addition, SWO-38 cells were incubated in TRAIL （300 μg/L）, mevastatin （30 μmol/L）, and a solution containing both TRAIL and mevastatin for 12, 24, 48 and 72 hours. MAIN OUTCOME MEASURES： Cell proliferation was detected using methyl thiazolyl tetrazolium assay; cell apoptosis was observed using Hoechst 33258 staining and fluorescence microscopy and was measured using Annexin V/propidium iodide flow cytometry; TRAIL R1/DR4 and TRAIL R2/DR5 protein expressions levels were measured using indirect immunofluorescence staining combined with flow cytometry in the recombinant soluble TRAIL （rsTRAIL, 300 tJg/L）, mevastatin （30 IJmol/L） and combination groups; TRAIL R1/DR4 and TRAIL R2/DR5 mRNA expression was detected using real-time polymerase chain reaction. RESULTS： rsTRAIL, mevastatin and their combination inhibited tumor proliferation in a time- and dose-dependent manner. The proliferation inhibitory rate and apoptosis rate of human SWO-38 cells in the combined group were significantly greater than the rsTRAIL or mevastatin alone group （P 〈 0.01）. TRAIL R1/DR4 and TRAIL R2/DR5 protein and mRNA expressions were increased in the combination group compared with mevastatin or rsTRAIL alone after 72 hours （P 〈 0.01）. CONCLUSION： Both rsTRAIL and mevastatin inhibit the proliferation and apoptosis of the human glioma cell line SWO-38, while their combination enhances the anti-tumor effect. The mechanism of action possibly correlates to the upregulation of TRAIL R1/DR4 and TRAIL R2/DR5 mRNA expression by mevastatin, thereby enhancing the cell sensitivity to rsTRAIL.

Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in glioma U87 cells

Studies have shown that tumor necrosis factor-related apoptosis-inducing ligand（TRAIL）exhibits strong induction of apoptosis in human glioma cells.It remains unclear whether the mitochondrion pathway,an important apoptosis signaling pathway,is involved in TRAIL-induced glioma cell apoptosis.In the present study,in vitro cultured human glioma U87 cells were treated with human recombinant soluble TRAIL.Apoptosis of glioma U87 cells,mitochondrial transmembrane potential（Δψm）,cytoplasmic cytochrome c concentration and changes in caspase-3,-8 and-9 activity following human recombinant soluble TRAIL treatment were investigated to determine the mechanism of glioma U87 cell apoptosis induced by TRAIL.Additionally,blocking caspase-8resulted in TRAIL-induced mitochondrion pathway activation,suggesting that TRAIL,through activating caspase-8,initiated a series of mitochondrial events and resulted in apoptosis of glioma U87 cells.

Polyphyllin Ⅰ enhances tumor necrosis factor-related apoptosis-inducing ligand-induced inhibition of human osteosarcoma cell growth via downregulating the Wnt/β-catenin pathway

OBJECTIVE:To investigate the synergistic effects of polyphyllin Ⅰ(PPⅠ)combined with tumor necrosis factorrelated apoptosis-inducing ligand(TRAIL)on the growth of osteosarcoma cells through downregulating the Wnt/β-catenin signaling pathway.METHODS:Cell viability,apoptosis and cell cycle distribution were examined using cell counting kit-8 and flow cytometry assays.The morphology of cancer cells was observed with inverted phase contrast microscope.The migration and invasion abilities were examined by xCELLigence real time cell analysis DP system and transwell assays.The expressions of poly(adenosine diphosphate-ribose)polymerase,C-Myc,Cyclin B1,cyclin-dependent kinases 1,N-cadherin,Vimentin,Active-β-catenin,β-catenin,p-glycogen synthase kinase 3β(GSK-3β)and GSK-3βwere determined by Western blotting assay.RESULTS:PPⅠ sensitized TRAIL-induced decrease of viability,migration and invasion,as well as increase of apoptosis and cell cycle arrest of MG-63 and U-2 OS osteosarcoma cells.The synergistic effect of PPⅠwith TRAIL in inhibiting the growth of osteosarcoma cells was at least partially realized through the inactivation of Wnt/β-catenin signaling pathway.CONCLUSION:The combination of PPⅠ and TRAIL is potentially a novel treatment strategy of osteosarcoma.

Induction of apoptosis in osteogenic sarcoma cells by combination of tumor necrosis factor-related apoptosis inducing ligand and chemotherapeutic agents

Background Osteosarcoma is one of the most common primary malignant tumors of bone with poor prognosis. TNF-related apoptosis inducing ligand （TRAIL） is a member of the tumor necrosis factor （TNF） cytokine family. TRAIL induces apoptosis in various tumor cell lines but is not found to be cytotoxic to many normal cell types in vitro. We investigated the cytotoxic activity of TRAIL and chemotherapeutic agents, including methotrexate （MTX）, doxorubicin （DOX） and cisplatin （CDDP）, on established osteosarcoma cell line-OS-732. Methods OS-732 cells were incubated with chemotherapeutic agents MTX,DOX and CDDP at various peak plasma concentrations（PPC）, 0.1PPC,1PPC and 10PPC, alone or with 100 ng/ml of TRAIL for 24 hours or 48 hours. MTT was used to evaluate the cytotoxic activity of different agents on OS-732. The apoptosis proportion was assayed by flow cytometry. Cellular morphologic changes were observed by phase contrast microscope, scan electron microscope, and transmission electron microscope. Results The inhibitory rate was （24.438±3.414）% with TRAIL of 100 ng/ml for 24 hours. The cells were responsive to DOX and CDDP with a dose-effect relationship （P〈0.05）. In OS-732 cells, DOX and CDDP cooperated synergistically with TRAIL when incubated the cells with them for 24 hours （the combined inhibitory rate is （58.360±2.146）% and （54.101±-2.721）%, respectively）. TRAIL alone or drugs alone induced the apoptosis rate was less than 25% （P〈0.05）. However, the combination of TRAIL and MTX did not present synergistic effects on OS-732 cells （P〉0.05, compared with TRAIL alone）. Conclusions Osteosarcoma OS-732 cells were not responsive to TRAIL-induced apoptosis. DOX and CDDP sensitize osteosarcoma OS-732 cells to TRAIL-induced apoptosis. The combination of TRAIL and MTX presented no synergistic effects on killing OS-732 cells.

经济发展阶段、要素条件变化与区域产业演化路径:后发国家视角

演化经济地理学将知识与技术置于分析的核心位置,重点关注技术关联在发达国家区域产业演化中的重要作用。然而,对后发国家来说,劳动力与资本等要素条件处于动态变化之中,会影响技术关联的作用。本文以演化经济地理学理论为基础,吸收相关经济学理论的合理成份,构建1个新的分析框架,探讨区域产业演化路径的阶段性调整。本文将经济发展阶段划分为刘易斯二元经济阶段、越过刘易斯转折点后阶段和创新发展阶段,从刘易斯二元经济理论、增长理论、后发国家赶超理论和新熊彼特主义演化经济学等理论中提取3个经济发展阶段生产要素的主要变动特征,在此基础上分析不同发展阶段要素条件变化与技术关联综合影响下的区域产业演化路径。本文研究结果可对后发国家区域产业演化提供一定启示。

高速公路建设费用影响因素及控制措施

为了更加合理地控制高速公路建设费用,在系统调查中国31个省份高速公路建设费用的基础上,深入研究了建设时期、路基宽度、桥隧比、设计速度和车道数目等因素对高速公路建设费用的影响规律,运用统计学和灰色理论定量地分析了各因素对建设费用的影响程度,并针对国家政策、新理念、价格因素、征地拆迁、工期变化、工程变更和地形条件等因素所造成的建设费用攀升提出控制措施。研究结果表明,各因素对高速公路建设费用的影响从大到小排序为:在山岭区是桥隧比、路基宽度和设计速度、总工期、建设开工时期;在平原区是路基宽度和设计速度、建设开工时期、总工期。

TRAIL-induced apoptosis of hepatocellular carcinoma cells is augmented by targeted therapies

AIM:To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors,in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand(TRAIL),on overcoming TRAIL resistance in hepatocellular carcinoma(HCC)and to study the efficacy of agonistic TRAIL antibodies,as well as the commitment of antiapoptotic BCL-2 proteins, in TRAIL-induced apoptosis. METHODS:Surface expression of TRAIL receptors (TRAIL-R1-4)and expression levels of the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL were analyzed by flow cytometry and Western blotting,respectively. Knock-down of MCL-1 and BCL-xL was performed by transfecting specific small interfering RNAs.HCC cellswere treated with kinase inhibitors and chemotherapeutic drugs.Apoptosis induction and cell viability were analyzed via flow cytometry and 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS:TRAIL-R1 and-R2 were profoundly expressed on the HCC cell lines Huh7 and Hep-G2. However,treatment of Huh7 and Hep-G2 with TRAIL and agonistic antibodies only induced minor apoptosis rates.Apoptosis resistance towards TRAIL could be considerably reduced by adding the chemotherapeutic drugs 5-fluorouracil and doxorubicin as well as the kinase inhibitors LY294002[inhibition of phosphoinositol- 3-kinase(PI3K)],AG1478(epidermal growth factor receptor kinase),PD98059(MEK1),rapamycin(mam- malian target of rapamycin)and the multi-kinase inhibitor Sorafenib.Furthermore,the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL play a major role in TRAIL resistance:knock-down by RNA interference increased TRAIL-induced apoptosis of HCC cells.Additionally, knock-down of MCL-1 and BCL-xL led to a significant sensitization of HCC cells towards inhibition of both c-Jun N-terminal kinase and PI3K.CONCLUSION:Our data identify the blockage of survival kinases,combination with chemotherapeutic drugs and targeting of antiapoptotic BCL-2 proteins as promising ways to overcome TRAIL resistance in HCC.

Downregulation of cyclooxygenase-1 is involved in gastric mucosal apoptosis via death signaling in portal hypertensive rats

Portal hypertension （PHT） gastropathy is a frequent complication of fiver cirrhosis and one of the leading causes of death from cirrhosis. Apoptosis is widely considered to be an active energy-dependent mode of cell death and a distinct entity from necrotic cell death. It is unclear whether gastric mucosal apoptosis is involved in PHT gastropa- thy. Prostaglandins （PGs） produced through cyclooxygenase （COX） are thought to play a key role in protection of the gastrointestinal mucosa from injury and apoptosis. However, the role of COX in PHT gastropathy is still not clearly understood. The aims of this study were to investigate whether （1） gastric mucosal apoptosis is involved in PHT gas- tropathy and （2） downregulation of COX contributes to this apoptosis. In this study, we show that gastric mucosal apoptosis was remarkably increased while mucosal proliferation was inhibited in PHT rats. Gastric mucosal COX- 1 was significantly suppressed at both the mRNA and protein levels, and PGE2 was reduced in PHT rats. Further, PGE2 treatment suppressed gastric mucosal apoptosis in PHT rats. However, gastric mucosal COX-2 levels did not differ between sham-operated rats and PHT rats. Gastric mucosal levels of tumor necrosis factor-α （TNF-α） and Fas ligand, but not TNF-related apoptosis-inducing ligand, were increased, and activated caspase-8 and caspase-3 levels were upregulated in PHT rats. The release of cytochrome c from the mitochondria to the cytosol was not observed in PHT rats. Our data indicate that downregulation of COX-1 is involved in gastric mucosal apoptosis via death signal- ing-mediated type-I cell death in PHT rats.

Bcl-2 degradation is an additional pro-apoptotic effect of polo-like kinase inhibition in cholangiocarcinoma cells

To examine the influence on apoptotic mechanisms following inhibition of polo-like kinases as therapeutically approach for cholangiocellular cancer treatment.METHODSAs most cholangiocarcinomas are chemotherapy-resistant due to mechanisms preventing tumor cell death, we investigated the effect of Cisplatin on cholangiocellular carcinoma (CCA) cell lines KMCH-1 and Mz-Ch-1. Polo-like kinases (PLK) are important regulators of the cell cycle and their inhibition is discussed as a potential therapy while PLK inhibition can regulate apoptotic mediators. Here, cells were treated with PLK inhibitor BI6727 (Volasertib), Cisplatin, and in combination of both compounds. Cell viability was assessed by MTT; apoptosis was measured by DAPI staining and caspase-3/-7 assay. Western blot and qRT-PCR were used to measure expression levels of apoptosis-related molecules Bax and Bcl-2.RESULTSThe cell viability in the CCA cell lines KMCH-1 and Mz-Ch-1 was reduced in all treatment conditions compared to vehicle-treated cells. Co-treatment with BI6727 and cisplatin could even enhance the cytotoxic effect of cisplatin single treatment. Thus, co-treatment of cisplatin with BI6727 could slightly enhance the cytotoxic effect of the cisplatin in both cell lines whereas there was evidence of increased apoptosis induction solely in Mz-Ch-1 as compared to KMCH-1. Moreover, PLK inhibition decreases protein levels of Bcl-2; an effect that can be reversed by the proteasomal degradation inhibitor MG-132. In contrast, protein levels of Bax were not found to be altered by PLK inhibition. These findings indicate that cytotoxic effects of Cisplatin in Mz-Ch-1 cells can be enhanced by cotreatment with BI6727.CONCLUSIONIn conclusion, BI6727 treatment can sensitize CCA cells to cisplatin-induced apoptosis with proteasomal Bcl-2 degradation as an additional pro-apoptotic effect.

岷江上游干旱河谷区植被多样性与环境因子的相关性研究

对岷江上游干旱河谷区植被多样性与环境因子相关研究表明:1)阴、阳坡灌、草丛植物群落物种α多样性指标均随海拔升高表现出明显的增加趋势,阳坡呈现出中间低两头高的海拔梯度格局;阴坡总体呈现直线上升的趋势。2)该区土壤肥力总体水平高低表现为:中上部>中部>下部>中下部、阴坡>阳坡。低海拔地区土壤破碎,土壤含水量和土壤肥力极低,高海拔地区的土壤水分含量和土壤肥力都相对较高,立地条件也较适宜植物的生长。3)植被多样性与环境因子的相关分析表明,海拔、坡向、坡度、土壤含水量、速效N、速效K、有机质、全N、全K与灌丛群落多样性和生物量均呈正相关关系,而pH值、速效P、全P、全Ca与多样性和生物量呈负相关关系。通过逐步回归分析和主成分分析筛选出环境主导因子为全N、速效P、土壤含水量和速效N。

重庆四面山常绿阔叶林种子库与生态因子灰色关联度分析

用“灰色关联分析法”研究了种子库大小与生态因子间关联的程度．结果表明，不同海拔高度种子库的大小与土壤厚度、枯落物厚度、地上植物种类关联度最大；同一海拔高度种子库的大小与土壤厚度、枯落物厚度关联度最大．对主导因子的分析结果表明，同一海拔高度的生态因子间比不同海拔高度的生态因子间具有更高的关联度；不同海拔高度的生态因子中受其它因子影响最大的是土壤ｐＨ值和枯落物厚度；相同海拔高度的生态因子中受其它因子影响最大的是土壤厚度．

EGCG Enhances TRAIL-mediated Apoptosis in Human Melanoma A375 Cell Line

Tumor necrosis factor-related apoptosis-inducing ligand （TRAIL） is a promising anti-cancer agent. Epigallocatechin-3-gallate （EGCG） is a polyphenolic constituent of green tea. In this study, inhibitory effect of combined use of EGCG and TRAIL on human melanoma A375 cells was examined and the possible mechanism investigated. The cells were divided into 4 groups： control group, EGCG group （EGCG： 10, 20 μg/mL）, TRAIL group （TRAIL： 25 ng/mL） and EGCG＋TRAIL group （combined group）. The growth inhibition was measured in the A375 cells treated with different concentrations of TRAIL （（25, 50, 75, 100, 125, 150 ng/mL） by MTT assay. The apoptosis was assessed by flow cytometry. The expressions of DR4 and DR5 were detected by flow cytometry and western blotting. The activities of caspase-8 and caspase-3 were determined by colorimetric assay. The results showed that TRAIL could dose-dependently inhibit the growth of A375 cells and the IC50 of TRAIL was 150 ng/mL. The apoptosis rate was 11.8% in the TRAIL group, 5%–7% in the EGCG group and 48.9%–59.1% in the combined group. Significant difference was found in the apoptosis rate between the combined group and the EGCG or TRAIL group （P〈0.05 for each）. The expression of DR4 instead of DR5 was significantly increased in the EGCG group. The activity of caspase-3 rather than caspase-8 was substantially enhanced in the EGCG group. These results suggest that EGCG is useful for the TRAIL-based treatment for melanoma.

重庆四面山珍稀濒危植物与环境因子的关联度分析

运用灰色系统理论的关联度分析法对重庆四面山部分珍稀濒危植物的分布和生长与其环境间的相互关系进行了尝试性研究．选择该地区分布较广的８种珍稀濒危植物作为目标集（母因子集），与之对应的９个环境因子作为因素集（子因子集）．分析结果表明，８种珍稀濒危植物受影响最大的环境因子分别是：福建柏—种丰富度；鹅掌楸、八角莲—土壤有机质；银杏、厚朴—人为干扰度；杜仲—土壤厚度；黄连、天麻—海拔高度．８种珍稀濒危植物受９种环境因子的综合影响程度由大到小的潜在序列为杜仲＞福建柏＞天麻＝黄连＞银杏＞八角莲＞鹅掌楸＞厚朴．

基于不同尺度和模型的小秦岭谱系结构研究

为探索研究尺度、零模型与群落谱系结构的关系,在小秦岭自然保护区建立1 hm^2样地,运用约束型、非约束型零模型分别从10、20、25 m 3个研究尺度上分析群落谱系结构,结果表明:(1)非约束型模型下,谱系结构聚集;约束型模型下,10、20 m尺度上,谱系聚集,25 m尺度上谱系分散。对比发现,随研究尺度增大,谱系聚集程度降低,趋于分散,可能是由于环境异质性对物种分布的影响程度降低,密度制约作用增强所致。(2)空间因子对谱系结构的影响远远大于地形因子,随研究尺度增加,空间因子及地形因子的解释量逐渐增大。地形的不同营造了不同的空间差异,二者密切相关。因此,空间因子是影响谱系结构形成的直接因素,而地形因子是间接因素。

Expression of caspase-3 and TRAIL receptors in CD4^+ and CD8^+ T cells of SLE patients

Objective: To study the expression of caspase-3 and tumor necrosis factor-related apoptosisinducing ligand (TRAIL) receptors in the CD4+ and CD8+ T cells of systemic lupus enythematosus (SLE) patients. Methods: RT-PCR was used to analyze the expression of caspase-3 and TRAIL receptors in CD4+ and CD8+ T cells of SLE patients and normal subjects. Results: The death domain-containing TRAIL-R1/R2 as well as 'decoy' TRAIL-R3/R4 were co-expressed in majority of CD4+ and CD8+ T cells in both SLE patients and normal subjects. The CD8+ T cells from SLE patients showed significantly higher expression of caspase-3 and TRAIL-R2 than those from normal subjects,and the expression was correlated with the activity of the disease. Conclusion: The TRAIL-R2 signal pathway might contribute to the apoptosis of T cells in SLE.

在线零售情境因素对顾客惠顾意愿的影响研究

作为新兴的零售渠道,互联网在零售业中的重要性日益凸显.随着在线零售业竞争的不断加剧,零售商越来越重视在线商店的情境因素对顾客惠顾的影响.从自我决定理论的视角,考察了在线零售情境中的产品相关情境因素和市场相关情境因素如何影响顾客在网上购物活动中的自主需要满足和关系需要满足,进而影响顾客的惠顾意愿;研究进一步提出了情境因素影响顾客惠顾意愿的两种内部化机制,即感知控制和感知兴趣.研究结论有助于深入理解在线零售情境因素对顾客惠顾意愿的影响作用,并为在线零售商提供了设计在线零售情境因素的新视角.

南充市近郊退化灌丛草坡群落物种多样性与环境因子灰色关联度分析

用灰色系统理论的关联度分析对南充近郊退化灌丛草坡群落的物种多样性及其与生态因子的相关性进行了研究．基本方法是按典型样方法进行实地取样测定．结果表明南充近郊退化灌丛草坡群落的８个因子对４个多样性指数即香农指数Ｈ′，辛普森指数λ，物种丰富度指数Ｎ０。

Piperlongumine inhibits cell growth and enhances TRAIL-induced apoptosis in prostate cancer cells

Objective: To investigate whether piperlongumine can sensitize prostate cancer cells to tumor necrosis factor-related apoptosisinducing ligand(TRAIL) and trigger apoptosis in prostate cells. Methods: Human prostate cancer cell lines PC3, LNCa P, and VCa P were cultured with piperlongumine and TRAIL. Then, cell proliferation, migration, caspase activation, apoptotic protein expressions, and death receptor expressions were measured.Results: Piperlongumine inhibited cell proliferation at low doses(<10 μM) alone and in combination with TRAIL(25 ng/m L), induced apoptosis, and suppressed cyclooxygenase activation. Additionally, piperlongumine induced expression of death receptors which potentiated TRAIL-induced apoptosis in cancer cells but did not affect decoy receptors. Piperlongumine also downregulated tumor cell-survival pathways, inhibited colony formation and migration of cancer cells alone or in combination with TRAIL. The combination of piperlongumine with TRAIL was found to be synergistic. Conclusions: Our findings indicate that piperlongumine can sensitize cancer cells to TRAIL through the upregulation of death receptors and can trigger apoptosis with the downregulation of antiapoptotic proteins.

Combination of oridonin and TRAIL induces apoptosis in uveal melanoma cells by upregulating DR5

AIM:To investigate the inhibitory effect of the combined use of tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)and oridonin on choroidal melanoma cell lines,and to explore its underlying mechanism.METHODS:MUM-2B and C918 cells were treated with different concentrations of TRAIL and oridonin,and MTT assay used to evaluate the inhibition rate of the two compounds on cells.Then,the cell cycle distribution and apoptosis were detected by flow cytometry,and changes in apoptosis-related proteins such as death receptor 5(DR5),a-caspase-3,and x-linked inhibitor of apoptosis protein(XIAP)were detected by Western blot.MUM-2B cells were transfected with si-DR5,which interfered with the expression of the DR5 gene.MTT and Western blot assay were used to detect cell activity and apoptosis-related proteins.RESULTS:When TRAIL and oridonin were simultaneously administered to the MUM-2B cells,the apoptosis rate was significantly higher than that by the two drugs individually.However,the effect of combined use of TRAIL and oridonin on C918 cells was not significantly different from that used alone.Cell cycle analysis showed that TRAIL and oridonin could induce G2/M arrest in MUM-2B cells.The Western blot results showed that the protein expression levels of the DR5,a-caspase-3,and BAX increased,while the expression levels of the anti-apoptosis-related proteins XIAP and BCL-2 were suppressed when TRAIL and oridonin simultaneously administered to MUM-2B cells.Interfering the expression of DR5 gene in MUM-2B cells could reverse the inhibitory effect of oridonin and TRAIL on the proliferation and apoptosis induction of MUM-2B cells.CONCLUSION:The inhibitory effects of oridonin and TRAIL on MUM-2B cells are significantly enhanced when they were administered as a combined treatment,which may ascribe to up-regulation of DR5.