芦荟大黄素介导的光动力疗法对人口腔黏膜癌KB细胞杀伤效果的研究

目的 探讨芦荟大黄素(Aloe-emodin,AE)介导的光动力疗法(Photodynamic therapy,PDT)对人口腔黏膜癌KB细胞的杀伤效果。方法 通过MTT法检测不同实验条件对KB细胞的杀伤作用。实验分为空白对照组(Control)、单纯药物组(AE)、单纯光照组(Laser)和光动力组(PDT)。分别比较AE组不同浓度(10μM、20μM、30μM和40μM)、Laser组不同光照时间(10s、20s、40s、80s)与Control组对KB细胞的杀伤作用,分析PDT组AE浓度和时间对KB细胞杀伤作用的影响。结果 与Control组相比,AE组和Laser组对KB细胞的杀伤作用无统计学意义(P＞0.05)。PDT组对KB细胞的杀伤作用呈浓度和时间依赖性,当AE的浓度为40μM,照射时间为80s时,细胞存活率降低至56.7%。结论 AE介导的PDT对KB细胞有显著的杀伤作用。     

TRAIL与阿霉素联用协同杀伤人结肠癌细胞SW480

背景与目的:肿瘤坏死因子相关凋亡诱导配体(tumornecrosisfactor-relatedapoptosisinducingligand,TRAIL)可选择性杀伤肿瘤细胞,而不影响正常细胞生长。当一部分肿瘤细胞对TRAIL不敏感时,特定的其它药物可增强其杀伤作用。本文旨在探讨结肠癌细胞SW480对TRAIL的敏感性,以及TRAIL与阿霉素联用对细胞的杀伤作用及可能作用机制。方法:常规培养结肠癌细胞SW480。利用MTT法检测细胞毒性作用,流式细胞术定量分析凋亡细胞比例,透射电镜在亚细胞结构形态上证实凋亡细胞,Westernblot分析p53及bcl-2蛋白表达变化。结果:(1)SW480细胞对TRAIL不敏感,100ng/mlTRAIL只能杀伤7.8%的细胞,IC50>1000ng/ml,且不存在浓度依赖性。(2)SW480细胞对阿霉素敏感,存在浓度依赖性作用,IC50=65μmol/L,0.86μmol/L的阿霉素对细胞不表现杀伤作用。(3)TRAIL与阿霉素合用表现出协同作用,亚毒性浓度TRAIL(100ng/ml)与亚毒性浓度阿霉素(0.86μmol/L)联用可杀伤80%SW480细胞。流式细胞学证实这种杀伤作用主要通过诱导细胞凋亡实现,透射电镜亦观察到大量凋亡细胞存在。药物作用前后,p53及bcl-2蛋白表达水平无明显改变。结论:结肠癌细胞株SW480对TRAIL不敏感,但TRAIL与亚毒性浓度阿霉素联用对癌细胞有协同杀伤作用,这种细胞毒性作用主要表现     

银环蛇毒素对白血病K562细胞株的毒性作用研究

目的　探讨银环蛇毒素及其若干组分在体外对白血病K5 6 2细胞株的毒性作用。方法　采用阳离子交换层析法分离纯化银环蛇粗毒 ,应用MTT法、流式细胞术等研究毒素对K5 6 2细胞株的杀伤和凋亡作用。结果　研究发现 ,银环蛇毒素在浓度超过 8× 10 3 ng/ml后开始对K5 6 2细胞 (细胞密度约为 1.1× 10 6个 /ml)有杀伤作用 ,浓度为 8× 10 5ng/ml时已有非常强的杀伤作用。结论　这种杀伤作用具有时间和浓度依赖的关系 ,随着毒素处理时间的延长 ,毒素的K5 6 2细胞杀伤作用也越强 ,但是 ,银环蛇粗毒的这种杀伤作用并非是细胞凋亡作用。     

体外扩增肾癌患者自体NK细胞及其对人肾细胞癌786-O细胞的杀伤

目的:探究IL-15、4-1BBL基因修饰的人白血病K562细胞(modi-K562细胞)联合IL-2体外高效扩增肾细胞癌患者自体自然杀伤(natural killer,NK)细胞的方法,研究扩增前后NK细胞对肾癌细胞株786-O的杀伤作用。方法:10例肾癌患者的外周血单个核细胞(peripheral blood mononuclear cell,PBMC)与modi-K562细胞在含不同浓度IL-2培养液中共育14 d,采用流式细胞术、Calcein-AM释放实验检测NK细胞的扩增情况、免疫表型及对肾癌786-O细胞的杀伤作用。结果:modi-K562细胞联合IL-2可有效扩增NK细胞,300 U/ml IL-2培养14 d时,NK细胞扩增(202.4±12.8)倍。在效靶比为20∶1时,扩增后NK细胞对786-O细胞的杀伤率为(72.0±4.3)%,显著高于扩增前NK细胞的杀伤率(34.2±3.6)%(P<0.01)。结论:IL-15、4-1BBL基因修饰的K562细胞联合IL-2在体外能有效扩增肾细胞癌患者NK细胞,扩增后NK细胞对肾癌786-O细胞的杀伤作用显著增强。     

抗白血病树突状细胞疫苗的制备

目的探索抗白血病异体树突状细胞疫苗的制备方法.方法从健康者外周血中诱生DC,用不同方法负载K562抗原(化学融合法,冻融抗原冲击法,肿瘤与DC共培养法),比较这些DC疫苗在递呈抗原激活T细胞增殖及杀伤功能方面的差异.结果从健康者外周血中可诱生出具有正常免疫表型和抗原递呈功能的DC.不同抗原负载方法致敏的DC均能激活T细胞特异性杀伤K562细胞.冻融抗原负载的DC能有效刺激T细胞增殖,其活化的CTL对K562的杀伤毒性最强.结论异体DC可有效递呈肿瘤抗原,激活T细胞杀伤肿瘤,冻融抗原负载的DC激活T细胞对肿瘤的杀伤最强,为今后临床DC疫苗的选择提供了实验依据.     

Evaluation of a modified culture method for immune-killer cells and therapeutic efficiency on hepatocarcinoma cell line BEL-7402

目的:探讨免疫杀手细胞(immune-killer cells,IKCs)的体外扩增方法及其对人肝癌细胞BEL-7402的杀伤作用.方法:改良自然杀伤细胞培养扩增法扩增IKCs细胞,流式细胞仪分析IKCs表型,台盼蓝染色计数法观察细胞增殖状况,Alamar Blue法观察IKCs细胞对BEL-7402细胞的杀伤作用,用BALB/c裸鼠模型检测IKCs细胞对肝癌动物模型的治疗作用.结果:IKCs细胞培养14d的细胞总数扩增300倍以上,主要由CD3+CD56+、CD3-CD56+和CD8+细胞亚群组成,CD3+CD56+和CD3-CD56+比例达85％以上,CD8+比例达到77％以上.IKCs细胞对肝癌BEL-7402细胞的杀伤实验显示,当效靶比为25∶1时和100∶1时,其杀伤活性分别为66.5％和97.8％(P＜ 0.01).裸鼠肝瘤模型治疗实验显示,IKCs细胞对早期和晚期人肝癌BEL-7402细胞裸鼠模型均有显著的治疗作用,与对照组比较,其抑瘤率达69％以上(P＜0.01).结论:本实验建立的肿瘤免疫杀手细胞IKCs的培养扩增方法是可行的、有效的,有望成为一种新的肿瘤免疫细胞治疗方法.     

预激态补骨脂素对白血病原代细胞杀伤作用的研究

目的:体外观察预激态补骨脂素(PAP)对白血病原代细胞的杀伤作用。方法:6例临床确诊为白血病的血标本采用体外细胞培养方法,在白血病原代细胞培养板中加入PAP,使其浓度保持在0.05g/L。短期用药PAP浓度维持24h,7天时终止实验;长期用药PAP浓度维持5天,并分别在第7天、第10天、第14天时终止实验。以细胞总数、台盼蓝拒染率和台盼蓝拒染细胞抑制率等作为检测指标,以配对t检验进行组间比较。结果:短期用药和长期用药均显示PAP对白血病原代细胞具有显著杀伤作用。短期用药(≤7天),作用时间延长对PAP杀伤白血病细胞作用的影响不明确。长期用药结果显示台盼蓝拒染细胞抑制率从32.40%～69.50%升至94.10%～98.90%。难治或耐药与否对PAP杀伤白血病细胞作用无明显影响。结论:PAP对白血病原代细胞具有显著的杀伤作用,有可能成为一广谱抗白血病药物。     

免疫杀手细胞的体外扩增方法及其对肝癌细胞BEL-7402的杀伤作用

目的:探讨免疫杀手细胞(immune-killer cells,IKCs)的体外扩增方法及其对人肝癌细胞BEL-7402的杀伤作用。方法:改良自然杀伤细胞培养扩增法扩增IKCs细胞,流式细胞仪分析IKCs表型,台盼蓝染色计数法观察细胞增殖状况,AlamarBlue法观察IKCs细胞对BEL-7402细胞的杀伤作用,用BALB/c裸鼠模型检测IKCs细胞对肝癌动物模型的治疗作用。结果:IKCs细胞培养14 d的细胞总数扩增300倍以上,主要由CD3~+CD56~+、CD3~-CD56~+和CD8~+细胞亚群组成,CD3~+CD56~+和CD3~-CD56~+比例达85%以上,CD8~+比例达到77%以上。IKCs细胞对肝癌BEL-7402细胞的杀伤实验显示,当效靶比为25:1时和100:1时,其杀伤活性分别为66.5%和97.8%(P<0.01)。裸鼠肝瘤模型治疗实验显示,IKCs细胞对早期和晚期人肝癌BEL-7402细胞裸鼠模型均有显著的治疗作用,与对照组比较,其抑瘤率达69%以上(P<0.01)。结论:本实验建立的肿瘤免疫杀手细胞IKCs的培养扩增方法是可行的、有效的,有望成为一种新的肿瘤免疫细胞治疗方法。     

红细胞与LAK细胞共培养上清对Raji细胞的细胞毒作用

目的 研究人红细胞(RBC)对LAK细胞杀伤活性的影响及RBC及LAK细胞共培养上清(R—LAK—S)对Raji细胞的细胞毒作用。方法 采用MTT比色法测定LAK细胞的杀伤活性和R—LAK—S的细胞毒性。结果 不同浓度的RBC对LAK细胞的杀伤活性都有促进作用(P<0.01),随着RBC浓度的增加,其促进作用加强。不同RBC:PBMC比例的R—LAK—S对Raji细胞均有细胞毒性,且随RBC浓度的增加以及与Raji细胞作用时间的延长,其对Raji细胞的细胞毒也增强。结论 人RBC能增强LAK细胞的杀伤活性,R—LAK—S对Raji细胞有细胞毒性。     

纳米羟基磷灰石对人骨肉瘤细胞U2OS增殖和凋亡的影响

目的:探索纳米羟基磷灰石（Nano-HAP）对人骨肉瘤细胞U2OS增殖和凋亡的影响。方法:不同浓度的Nano-HAP处理人骨肉瘤细胞U2OS后,通过FDA染色检测Nano-HAP对细胞黏附的影响;CCK8实验和克隆形成实验检测Nano-HAP对细胞生长增殖的影响;最后利用Annexinv-FITC凋亡检测试剂盒检测Nano-HAP对细胞凋亡的影响。结果:不同浓度的Nano-HAP对U2OS的黏附没有显著影响,但是对U2OS的克隆形成具有显著抑制作用,同时在50 μg/ml 和800 μg/ml时,可以显著抑制骨肉瘤细胞U2OS的增殖。结论:Nano-HAP对骨肉瘤细胞具有显著的抑制增殖促进凋亡作用,但效应与纳米粒子浓度并无直接的线性关系。     

Cyclin D3 is a predictive and prognostic factor in diffuse large B-cell lymphoma.

Cyclin D3 is an important regulator for transition from G(1) to the S phase of the cell cycle. Cyclin D3 expression is associated with cell proliferation in lymphoid tissues, but its impact on clinical outcome in non-Hodgkin's lymphomas has not been studied. Therefore, we determined the clinical relevance of cyclin D3 expression in patients with diffuse large B-cell lymphoma. We examined the relation between cyclin D3 expression at diagnosis and response to conventional polychemotherapy and overall survival in 81 previously untreated patients with diffuse large B-cell lymphoma. Cyclin D3 expression was assessed by immunohistochemistry. Cyclin D3 immunostaining ranged from 0-100% (median, 30%) of the lymphoma cells. Patients with high (>or=50% cyclin D3-positive lymphoma cells) cyclin D3 expression had a more advanced clinical stage (P = 0.003) and more often had extranodal disease in more than one site (P = 0.007) than patients with low cyclin D3 expression. Patients with high cyclin D3 expression had a significantly lower complete response rate (17% versus 74%; P < 0.001) and a shorter overall survival (3-year survival rate, 18% versus 74%; P < 0.001) than those with low cyclin D3 expression. Multivariate analyses that included cyclin D3 and the International Prognostic Index demonstrated that cyclin D3 expression had independent effects on the complete response rates and overall survival of the patients. In conclusion, high cyclin D3 expression is an independent predictive and prognostic factor associated with poor clinical outcome in patients with diffuse large B-cell lymphoma.     

Novel HDAC inhibitors exhibit pre-clinical efficacy in lymphoma models and point to the importance of CDKN1A expression levels in mediating their anti-tumor response

We investigated the pre-clinical activities of two novel histone deacetylase inhibitors (HDACi), ITF-A and ITF-B, in a large panel of pre-clinical lymphoma models. The two compounds showed a dose-dependent anti-proliferative activity in the majority of cell lines. Gene expression profiling (GEP) of diffuse large B-cell lymphoma (DLBCL) cells treated with the compounds showed a modulation of genes involved in chromatin structure, cell cycle progression, apoptosis, B-cell signaling, and genes encoding metallothioneins. Cell lines showed differences between the concentrations of ITF-A and ITF-B needed to cause anti-proliferative or cytotoxic activity, and cell cycle and apoptosis genes appeared implicated in determining the type of response. In particular, CDKN1A expression was higher in DLBCL cells that, to undergo apoptosis, required a much higher amount of drug than that necessary to induce only an anti-proliferative effect.In conclusion, the two novel HDACi ITF-A and ITF-B demonstrated anti-proliferative activity across different mature B-cell lymphoma cell lines. Basal CDKN1A levels appeared to be important in determining the gap between HDACi concentrations causing cell cycle arrest and those that lead to cell death.     

BET抑制剂对弥漫性大B细胞淋巴瘤细胞生长及外周血Th17细胞数量和相关细胞因子表达的影响

目的:探讨溴结构域和超末端结构域（bromodomain and extra terminal domain，BET）抑制剂对弥漫性大B细胞淋巴瘤CRL-2630细胞生长的影响，以及对弥漫性大B细胞淋巴瘤BALB/c-nu裸鼠外周血中辅助性T细胞17（helper T cells,Th17）数量和相关细胞因子表达的影响。方法:培养弥漫性大B细胞淋巴瘤株CRL-2630，使用不同浓度BET抑制剂（2、4、8、16、32 nmol/L）处理48 h，32 nmol/L BET抑制剂处理不同时间（12、24、36、48 h），CCK-8法检测各处理细胞活性；集落形成实验检测不同BET抑制剂浓度处理后细胞集落形成能力；Annexin V-FITC/PI双染法检测不同BET抑制剂浓度处理后细胞凋亡情况；实时荧光定量PCR与Western blot检测32 nmol/L BET抑制剂处理CRL-2630细胞48 h后HMGA1 mRNA与蛋白的表达水平；构建HMGA1过表达载体并通过脂质体介导法转染CRL-2630细胞，并用32 nmol/L BET抑制剂处理48 h，检测细胞活性与凋亡情况；构建裸鼠弥漫性大B细胞淋巴瘤模型并采集外周血，流式细胞术检测Th17细胞比例，ELISA法检测相关细胞因子的含量。结果:在一定范围内，BET抑制剂呈剂量依赖性地抑制CRL-2630细胞的活性，32 nmol/L BET抑制剂以时间依赖性地抑制CRL-2630细胞的活性。随着BET抑制剂处理浓度的增高，CRL-2630细胞集落形成能力逐渐下降，凋亡率逐渐升高。32 nmol/L BET抑制剂处理CRL-2630细胞48 h后，细胞中HMGA1的mRNA和蛋白水平均明显下降。pcDNA3.4-HMGA1转染CRL-2630细胞再使用BET抑制剂处理后，细胞的活性升高而凋亡率明显下降。弥漫性大B细胞淋巴瘤裸鼠经BET抑制剂作用后，外周血Th17细胞比例和IL-6、IL-17、IL-23含量较生理盐水组明显下降。结论:BET抑制剂能有效抑制 CRL-2630细胞活性，并诱导其凋亡，在一定范围内呈时效和量效关系。BET抑制剂还可以抑制弥漫性大B细胞淋巴瘤裸鼠外周血Th17细胞数量和相关细胞炎性因子的分泌，其作用机制可能与HMGA1的表达下调有关。     

Downregulation of Bfl-1 protein expression sensitizes malignant B cells to apoptosis

Elevated expression of the antiapoptotic protein Bfl-1 (A1) was previously reported in several cancer cell lines. Recently, molecular profiling of large B-cell lymphoma identified Bfl-1 as a gene signature in 'OxPhos' diffuse large B-cell lymphoma subtype and in primary mediastinal large B-cell lymphoma, suggesting that in addition to Bcl-2, Bcl-xL and Mcl-1, Bfl-1 may be a relevant target in the design of new strategies for cancer therapy. Using short hairpin RNA strategy, we show here that Bfl-1 silencing in one lymphoblastoid B-cell line and in two diffuse large B-cell lymphoma cell lines potently induces their apoptosis and sensitizes those cell lines to anti-CD20 (Rituximab)-mediated cell death as well as to apoptosis induced by chemotherapeutic molecules such as doxorubicin, vincristine, cisplatin and fludarabine. These results demonstrate for the first time that Bfl-1 is an essential protein for survival of malignant B cells and suggest Bfl-1 may represent a potential target for future drug development against B cell lymphoma.     

Increased apoptosis in B-chronic lymphocytic leukemia cells as a result of cyclin D3 down regulation

B-cell chronic lymphocytic leukemia (CLL) is a clonal B cell malignancy of morphologically mature, functionally immature B cells. B-cell CLL cells are known to be resistant to killing by anticancer and other agents. This resistance is associated with alterations in apoptosis and cell cycle regulated genes. In our earlier studies, we have demonstrated that CLL cells have differential expression of genes that are associated with apoptosis and cell cycle regulation, including elevated expression of Bcl-2, DAD-1, Cyclin D3 and cyclin dependent kinase 4 inhibitor. Therefore, in this study, in an attempt to study the role of Cyclin D3 in the resistant behavior of CLL cells, Cyclin D3 was down regulated using antisense oligonucleotide (AS-ODN) in WSU-CLL, a human CLL cell line. The down regulation of Cyclin D3 was confirmed by RT-PCR and flow cytometry techniques. The Cyclin D3 expression down-regulated WSU-CLL cells were then tested for their susceptibility to fludarabine, a chemotherapeutic agent. Our results showed that the Cyclin D3 expression down-regulated WSU-CLL cells were more susceptible to fludarabine mediated killing. Following treatment with fludarabine, there was a significant increase in the number of cells undergoing apoptosis in Cyclin D3 expression down-regulated WSU-CLL cells as determined by Annexin-V assay, cell cycle analysis for DNA content, and cytomorphology. Thus, our results indicate Cyclin D3 down regulation increases the killing of WSU-CLL cells with fludarabine by increasing the number of cells undergoing apoptosis.     

Cyclin D1和bcl-2在B细胞淋巴瘤中的表达及其在鉴别诊断中的意义

 B细胞淋巴瘤根据免疫表型可分为不同亚型,且不同亚型侵袭度不同,预后也有很大差异。Cyclin D1是已被证实与肿瘤有最直接关系的细胞周期蛋白,在大多B细胞淋巴瘤[套细胞淋巴瘤（MCL）、慢性淋巴细胞白血病（CLL）、边缘区淋巴瘤（MZL）、弥漫大B细胞淋巴瘤（DLBCL）等]中均有表达。多数B细胞淋巴瘤[滤泡性淋巴瘤（FL）、DLBCL等]都能可见易位活化的bcl-2表达增强。Cyclin D1及bcl-2作为B细胞淋巴瘤重要的细胞周期蛋白及抗凋亡基因,在淋巴瘤的鉴别诊断中起重要作用,其检测及检测手段的灵敏度和特异度具有重要的临床价值。     

利妥昔单抗与依鲁替尼对弥漫性大B细胞淋巴瘤细胞增殖和凋亡协同作用研究

目的 近年来发现依鲁替尼是B细胞恶性肿瘤的新型靶向药物,利妥昔单抗联合新药依鲁替尼对弥漫性大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)的研究逐步展开,本研究探讨利妥昔单抗与依鲁替尼对DLBCL细胞系Farage增殖及凋亡影响的协同作用.方法 不同浓度的单药利妥昔单抗和单药依鲁替尼处理Farage细胞24、48和72 h后,采用CCK8法检测细胞增殖抑制率.15 μmol/L依鲁替尼处理Farage细胞48 h后,采用RT-PCR法检测凋亡相关因子mRNA的表达变化.含人补体的培养条件下,1 μg/mL利妥昔单抗联合10 μmol/L依鲁替尼同时处理Farage细胞48 h后,采用CCK8法检测增殖抑制率,采用流式细胞术检测凋亡率.结果 利妥昔单抗在不含人补体的培养基中对Farage细胞增殖抑制作用不明显,在含人补体的培养基中有明显增殖抑制作用,并呈浓度和时间依赖性.依鲁替尼在含或不含人补体的培养条件下对Farage细胞均有明显增殖抑制作用,呈浓度和时间依赖性,2种条件下的增殖抑制率差异无统计学意义(F=0.978,P=0.329),15 μmol/L依鲁替尼作用Farage细胞48 h时,Fas(1.63±0.09)、Caspase-8(1.90±0.11)和Caspase-3(2.20±0.11)mRNA相对表达量均高于空白组(1.00±0.00).在含人补体的培养基中,1 μg/mL利妥昔单抗联合10 μmol/L依鲁替尼同时处理Farage细胞48 h后,联合组增殖抑制率为(57.06±1.48)%,高于依鲁替尼单药组(33.83±3.39)%和利妥昔单抗单药组(26.92±2.74)%,差异有统计学意义,F=87.403,P<0.001.联合组的凋亡和坏死率(44.30±2.20)%高于利妥昔单抗单药组(21.73±2.00)%和依鲁替尼单药组(17.44±1.60)%,且利妥昔单抗单药组和依鲁替尼单药组均高于空白组(2.32±0.21)%, 差异均有统计学意义,F=327.205,P<0.001.结论 利妥昔单抗可通过CDC效应引起DLBCL细胞凋亡坏死及增殖抑制,依鲁替尼可能通过上调Fas、Caspase-3和Caspase-8基因的表达,促使DLBCL细胞凋亡和增殖抑制,利妥昔单抗联合依鲁替尼对DLBCL细胞的增殖抑制和凋亡坏死作用明显强于单药利妥昔单抗或依鲁替尼.     

miR-155在弥漫性大B细胞淋巴瘤预后预测中的应用价值

目的:探讨miR-155在弥漫性大B细胞淋巴瘤预后预测中的应用价值。方法:选取我院收治的120例弥漫性大B细胞淋巴瘤作为研究对象,采用qRT-PCR检测所有患者癌组织miR-155的相对表达水平,根据miR-155的表达水平将所有患者分成miR-155高表达组（n=72）和miR-155低表达组（n=48）,比较两组患者的临床病理资料、生存率,采用 Cox比例风险回归模型对弥漫性大B细胞淋巴瘤患者的预后进行单因素和多因素分析,并分析miR-155对弥漫性大B细胞淋巴瘤细胞增殖和迁移能力的影响。结果:miR-155高表达组患者结外侵犯比例显著高于miR-155低表达组（P＜0.05）;miR-155高表达组患者3年无进展生存率（29.2%）及总体生存率（40.3%）均显著低于miR-155低表达组（81.3%和83.3%）;单因素和多因素分析结果均显示miR-155表达水平是DLBCL无进展生存期和总体生存期的影响因素;miR-155低表达组细胞划痕愈合速度(0.53±0.04)显著低于对照组细胞（1.0±0.03）(P＜0.05),miR-155低表达组细胞在培养的3、4 d的吸光度值显著低于对照组（0.38±0.01 vs 0.56±0.03;0.56±0.02 vs 0.76±0.02）（P＜0.05）。结论:弥漫性大B细胞淋巴瘤患者的miR-155表达水平显著影响患者的预后,其可能机制是通过影响弥漫性大B细胞淋巴瘤细胞的增殖和迁移能力,提示miR-155可能是弥漫性大B细胞淋巴瘤新的和可靠的预后生物标志物,值得进一步深入研究。     

Effect of BCLAF1 on HDAC inhibitor LMK-235-mediated apoptosis of diffuse large B cell lymphoma cells and its mechanism

Diffuse large B-cell lymphoma (DLBCL) is the most common type of adult lymphoma. It is a group of malignant tumors with a large number of clinical manifestations and prognoses. Therefore, it is necessary to explore its unknown potential therapeutic targets. Histone deacetylase inhibitor (HDACi) is a novel drug for the treatment of DLBCL, however pan-HDACis cannot be ignored because of their clinical efficacy. By contrast, specific HDACi is well-tolerated, and LMK-235 is a novel HDACi that is a specific inhibitor of HDAC4 and HDAC5. In this study, we investigated the up-regulation of BCLAF1 through NF-κB signaling pathways in LMK-235, mediating the apoptosis of two diffuse large B-cell lymphoma cell lines, OCI-LY10 and OCI-LY3. Further studies showed that BCLAF1 expression was increased in DLBCL cells after treatment with the NF-κB inhibitor Bay11-7082. The combination of Bay11-7082 and siRNA si-HDAC4 significantly increased BCLAF1 expression and further increased apoptosis. These results indicate that BCLAF1 plays an important role in LMK-235-mediated apoptosis and may be a potential target for the treatment of diffuse large B-cell lymphoma.