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凋亡蛋白抑制因子(inhibitor of apoptosis protein,IAP)是一类抑制凋亡的调节分子,其成员livin是新发现的凋亡抑制基因,存在同基因不同剪切的两个异构体:Livina和Livinβ;livin在多数肿瘤组织中高表达;其作用机制主要通过:1)抑制半胱天冬酶3/7/9(caspase3/7/9)的活性;2)激活TAK1/JNK1信号转导途径,同过非C途径抑制TNF及ICE诱导的细胞凋亡,来阻断细胞凋亡过程。livin与肿瘤发生有密切关系,并可能作为诱导肿瘤凋亡治疗的新靶点 相似文献
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Livin在肺癌中的表达及与pro-caspase3的相关性分析初步探讨 总被引:3,自引:0,他引:3
背景与目的Livin是凋亡抑制蛋白新成员之一,目前研究表明Livin在各种恶性肿瘤(包括肺癌)中过度表达,并促进肿瘤发生发展。本研究目的在于探讨在蛋白水平凋亡抑制蛋白livin在肺癌组织中的表达及与肺癌组织类型、术前化疗、淋巴结转移的关系;探索livin蛋白表达与pro-caspase3蛋白的关系。方法采用Western-blot方法检测肺癌组织及对照组中livin及pro-caspase3的蛋白水平的表达。结果27例肺癌组织中livin蛋白表达阳性率为55.6%(15/27),明显高于对照组癌旁组织(20.0%)和良性疾病肺组织(16.7%)(P<0.01)。其中在肺腺癌、鳞癌(包括大细胞癌)组织中livin蛋白阳性率分别为76.92%,38.46%,1例小细胞癌阴性;livin蛋白在术前有无化疗肺癌组织中及淋巴结有无转移组织中表达无明显差异(P>0.05)。应用凝胶成像仪测量各指标灰度值后显示,肺癌组织livin蛋白表达明显高于对照组(P<0.05);pro-caspase3蛋白在肺癌组织中表达高于对照组(P<0.01),livin蛋白表达与pro-caspase3蛋白表达呈正相关趋向。结论Livin蛋白可在不同病理类型肺癌组织中不同程度表达,livin蛋白表达与术前化疗及淋巴结转移无明显相关;livin蛋白表达与pro-caspase3蛋白呈正相关趋势,可能与其与pro-caspase3蛋白结合抑制其加工活化有关。 相似文献
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凋亡抑制蛋白(IAP)家族是一类重要的抗凋亡因子,与肿瘤的发生、发展密切相关.Livin选择性表达于多种常见的恶性肿瘤中,提示该基因可能在肿瘤形成过程中起重要作用.研究其生物学特性与功能及作用机制对于肿瘤的发生、发展、细胞耐药、肿瘤的治疗、预后等有重大意义.近年来对于以livin为靶点的基因与免疫治疗也成为热点研究之一,为肿瘤的综合治疗提供了新的策略和方向. 相似文献
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Livin异构体特异性基因沉默诱导肺腺癌SPC-A1细胞凋亡 总被引:5,自引:0,他引:5
目的:利用基因转染和RNA干涉(RNAi)技术,在SPC-A1细胞中建立Livin异构体α和β特异的基因沉默体系,探讨其在诱导SPC-A1细胞凋亡效应中的不同作用及价值。方法:在肺腺癌SPC-A1细胞中稳定表达Livinα β、Livinα和Livinβ特异性小干涉RNA(siRNA),观察SPC-A1细胞形态、增殖等生物学行为的改变,TUNEL法和流式细胞仪检测细胞凋亡率。结果:Livinα β、Livinα和Livinβ基因沉默后,SPC-A1细胞克隆形成能力较对照组显著下降(P<0.05);转染后SPC-A1细胞发生凋亡,TUNEL法显示细胞凋亡指数分别为(9.20±1.90)%、(6.75±1.20)%和(4.82±1.20)%,(流式细胞仪检测)细胞凋亡率分别为(7.48±1.30)%、(5.50±0.90)%和(4.16±0.70)%。结论:Livinα和β两种异构体均能作为诱导肺癌细胞凋亡的分子靶点,Livin基因沉默靶向诱导肺癌细胞凋亡可能作为手术、化疗、放疗等传统治疗的辅助手段。 相似文献
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目的:观察livin基因的siRNA对人胃癌细胞株BGC823生长与功能的影响.方法:构建针对livin基因siR-NA真核表达质粒pGPU6/GFP/Neo-livin,通过脂质体介导转染至BGC823细胞,半定量RT-PCR、蛋白质印迹法分别检测livin基因mRNA和蛋白表达,激酶活性检测试剂盒检测胱冬肽酶-3(Caspase-3)的活性,MTT法分别检测PBMC和BGC823细胞增殖活性,流式细胞仪检测细胞凋亡率,ELISA法检测混合细胞培养上清中TNF-α分泌量的变化.结果:转染48 h实验组细胞livin mRNA和蛋白表达水平明显受到抑制,表达抑制率分别为64.63%和62.80%,P<0.05;Caspase-3活性增强,细胞凋亡率为22.4%,P<0.05;PBMC和BGC823细胞增殖减慢;细胞培养上清中TNF-α分泌量明显降低,P<0.05.结论:通过抑制BGC823细胞中livin的表达,Caspase-3的活性增加,从而诱导细胞凋亡率上升;livin基因表达沉默可以抑制PBMC细胞增殖,TNF-α分泌减少,提示了livin基因可能是在细胞发生癌变初期过度表达的一个凋亡抑制基因. 相似文献
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Livin与肿瘤研究新进展 总被引:13,自引:2,他引:11
Livin是凋亡抑制蛋白家族的新成员,具有凋亡抑制蛋白家族的特征性结构——BIR结构域。这一结构域介导了Livin与Caspase-3、7、9的直接结合,从而阻断caspase凋亡作用的发挥,达到抑制细胞凋亡的作用。Livin基因定位于染色体20q13,编码Livinα和β两种蛋白。亚细胞定位显示,在细胞质和细胞核均有表达,羧基末端的RING结构域介导了Livin的亚细胞定位。目前的研究表明,Livin可表达于消化系统的胃癌、泌尿系统的膀胱癌、呼吸系统肺癌和血液系统的淋巴细胞性白血病等多个系统的肿瘤中,也存在于乳腺癌及黑色素瘤中,在肿瘤的细胞系中也有较广泛的表达,但在各系统的正常组织中却很少表达。研究还表明,在药物诱导凋亡时,Livin的表达有明显升高。用RNA干扰技术对Livin基因的表达进行干预后,细胞对诱导凋亡药物和放射线的敏感性增加。根据Livin设计的抗原肽可以特异性诱导肺癌患者杀伤性T细胞的活化。目前的研究已表明,Livin在肿瘤的发展和耐药中都有重要作用。Livin特异表达于肿瘤组织的特性有可能为肿瘤的早期诊断、基因治疗和细胞治疗提供新靶点。 相似文献
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慢病毒介导shRNA特异性沉默livin基因促进SPC-A1细胞凋亡 总被引:2,自引:0,他引:2
目的:建立慢病毒介导的livin基因沉默系统,探讨其对肺癌细胞凋亡的影响。方法:Livin shRNA慢病毒感染肺腺癌细胞株SPCA1沉默livin基因表达。应用PI染色经荧光镜下观察SPCA1细胞凋亡形态,流式细胞术检测SPCA1细胞凋亡率及亚二倍体峰形成,Realtime PCR及Western blotting方法检测livin和caspase 3表达的改变。结果:livin基因在肺腺癌细胞株SPCA1中持续高表达。经慢病毒介导shRNA使livin基因表达沉默后,镜下可见肺腺癌细胞出现典型凋亡形态特征,流式细胞术检测出现亚二倍体峰,细胞凋亡率较空白对照及阴性病毒对照细胞明显增加(8.21% vs 0.08%, 0.13%;P<0.05),RTPCR及Western blotting 检测结果显示,caspase 3 mRNA表达无改变,但cleavedcaspase 3蛋白表达上调。结论:慢病毒载体介导的shRNA能抑制肺腺癌细胞株SPCA1中livin基因的表达,从而促进SPCA1细胞凋亡。 相似文献
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Liu Chuan Wu Xiaohou Luo Chunli Hu Zili Yin Zhikang He Yunfeng Du Hu Zhang Weili Jiang Qing Lin Yanjun 《Journal of experimental & clinical cancer research : CR》2010,29(1):63
Background and Aim
in recent years, Livin, a new member of IAPs family, is found to be a key molecule in cancers. Researchers consider Livin may become a new target for tumor therapy; however, the role of it in bladder cancer is still unclear. The purpose of this article is to investigate Antisense Oligonucleotide (ASODN) of Livin on treating bladder cancer cell and underlying mechanisms.Methods
Phosphorathioate modifying was used to synthesize antisense oligonucleotides targeting Livin, followed by transfection into human bladder cancer cell 5637. After transfection, Livin mRNA and protein level, cell proliferation and apoptosis changes, caspase3 level and its effect on human bladder cancer transplantable tumor in nude mice were measured.Result
results showed Livin ASODN effectively inhibited Livin expression and tumor cell proliferation, and these effects probably through enhanced caspase3 activity and apoptosis of tumor cells. In nude mice transplantable tumor model, Livin expressions were inhibited meanwhile caspase3 expression was increased. Tumor growth slowed down and apoptosis was enhanced.Conclusion
Our data suggest that Livin plays an important role in inhibiting apoptosis of bladder cancer cells. Livin ASODN may promote cell apoptosis, inhibit bladder cancer growth, and become one of the methods of gene therapy for bladder cancer. 相似文献12.
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Aberrant expression and potency as a cancer immunotherapy target of inhibitor of apoptosis protein family, Livin/ML-IAP in lung cancer. 总被引:47,自引:0,他引:47
Hiroyuki Hariu Yoshihiko Hirohashi Toshihiko Torigoe Hiroko Asanuma Midori Hariu Yasuaki Tamura Katsuyuki Aketa Chika Nabeta Katsuya Nakanishi Kenjiro Kamiguchi Yoshinori Mano Hiroshi Kitamura Junichi Kobayashi Tomohide Tsukahara Noriharu Shijubo Noriyuki Sato 《Clinical cancer research》2005,11(3):1000-1009
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Silencing Livin gene expression to inhibit proliferation and enhance chemosensitivity in tumor cells
Wang R Lin F Wang X Gao P Dong K Zou AM Cheng SY Wei SH Zhang HZ 《Cancer gene therapy》2008,15(6):402-412
Livin, a novel member of the human inhibitors of apoptosis protein (IAP) family, plays an important role in tumor progression and occurrence by inhibiting cell apoptosis. It is selectively expressed in the most common human neoplasms and appears to be involved in tumor cell resistance to chemotherapeutic agents. To investigate its possibility as a therapeutic target for human malignancies, we established two genetically different stable tumor cell lines (LoVo and SPCA-1) and RNA interference (RNAi) technique was employed to downregulate Livin expression in two human tumor cell lines. The specific downregulation of Livin expression in tumor cell lines significantly inhibited in vitro cell proliferation and in vivo tumorigenicity. Furthermore, Livin knockdown led to cell arrest in the G(1)/G(0) phase of cell cycle, eventual apoptosis and chemosensitivity enhancement in tumor cells. All these results indicate that RNAi-mediated downregulation of Livin expression can lead to potent antitumor activity and chemosensitizing effects in human cancers. 相似文献
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目的:探讨凋亡抑制蛋白Livin在非小细胞肺癌组织和血清中的表达及其与组织类型、临床分期的关系。方法:采用免疫组化法和酶联免疫吸附法(ELISA)分别对40例肺癌组织和血清,20例癌旁组织和良性病变组织,20例健康者血清中Livin的表达水平进行检测。结果:非小细胞肺癌患者组织和血清中Livin水平明显高于对照组(P〈0.05);组织中Livin蛋白的表达与淋巴结转移有关,但与肺癌临床分期、病理类型、分化程度无关。血清中Livin水平与淋巴结转移、临床分期有关,但与病理类型、分化程度无关;组织和血清间Livin水平无相关性。结论:Livin作为一种新的凋亡抑制蛋白,对非小细胞肺癌诊断、淋巴结转移的判断具有一定的临床价值。 相似文献
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Livin, a novel member of the human inhibitors of apoptosis protein family, plays an important role in tumor progression and
occurrence by inhibiting cell apoptosis. It is selectively expressed in the most common human neoplasms and appears to be
involved in tumor cell resistance to chemotherapeutic agents. The present study was designed to investigate the potential
of using RNA interference (RNAi) technique to downregulate Livin expression, and the subsequent effect on human glioma cells.
The results showed that knockdown of Livin expression by short interfering RNA (siRNA) significantly inhibited glioma cell
proliferation and increased cell apoptosis through cell arrest in the G1/G0 phase of cell cycle in vitro. Furthermore, Livin siRNA significantly suppressed tumor growth in nude mice. Together, these
findings suggest that RNAi-mediated downregulation of Livin expression could lead to potent antitumor activity in glioma cells
and might serve as a novel therapeutic strategy in clinic. 相似文献
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《Asian Pacific journal of cancer prevention》2014,15(20):8577-8579
Osteosarcoma is a common malignant tumor of bone, but mechanisms underlying its development are stillunclear. At present, it is believed that the inhibition of normal apoptotic mechanisms is one of the reasons forthe development of tumors, so specific stimulation of tumor cell apoptosis can be considered as an importanttherapeutic method. Livin, as a member of the newly discovered inhibitor of apoptosis proteins (IAPs) family,has specifically high expression in tumor tissues and can inhibit tumor cell apoptosis through multiple ways,which can become a new target for malignant tumor treatment (including osteosarcoma) and might of greatsignificance in the clinical diagnosis of tumors and the screening of anti-tumor agents and carcinoma treatment. 相似文献