Silencing Livin gene expression to inhibit proliferation and enhance chemosensitivity in tumor cells

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.     

siRNA directed against Livin inhibits tumor growth and induces apoptosis in human glioma cells

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.     

Antisense oligonucleotide targeting Livin induces apoptosis of human bladder cancer cell via a mechanism involving caspase 3

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.     

凋亡抑制蛋白Livin在肿瘤治疗中的新进展

Livin是凋亡抑制蛋白的一个新成员,可以编码抑制凋亡的负性调节蛋白。Livin在大多数肿瘤中高表达,体内外研究发现其表达降低可以增加肿瘤细胞凋亡,降低肿瘤细胞的生长潜能,增加肿瘤细胞对化疗的敏感性。因此,Livin可以作为肿瘤治疗的新的靶点。     

凋亡抑制因子Livin在肺癌组织和血清中的表达

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。     

Livin反义寡核苷酸对人乳腺癌细胞株MCF-7增殖和凋亡影响的研究

目的：探讨Livin mRNA反义寡核苷酸（ASODN）对人乳腺癌MCF-7细胞抑制增殖及诱导凋亡的影响。方法：设计合成特异性的Livin硫代磷酸ASODN及其对照错义寡核苷酸（MSODN）,脂质体转染至培养的MCF-7细胞。采用MTT法检测Livin ASODN对MCF-7细胞的增殖抑制作用,RT-PCR检测Livin mRNA的表达水平,电镜、流式细胞仪与吖啶橙／溴化乙锭（AO／EB）细胞染色法检测细胞凋亡水平和形态学改变。结果：Livin ASODN在终浓度为600nmol／L作用MCF-7细胞48h时,能明显地抑制其增殖（IC50=604.4）,降低Livin mRNA的表达;电镜、流式细胞仪与A0／EB细胞染色法则表明MCF-7细胞在形态学上出现明显的凋亡改变,细胞凋亡率显著增加,而对照组寡核苷酸未见抑制效应。结论：Livin ASODN能够特异性下调MCF-7细胞中Livin基因表达,在诱导肿瘤细胞凋亡、抑制增殖中发挥重要作用。     

Livin基因在恶性肿瘤诊断和治疗中的研究

Livin是凋亡抑制蛋白家族最新的成员,通过抑制半胱氨酸天冬氨酸蛋白酶、激活丝裂原激活蛋白激酶等途径参与细胞凋亡的调节.Livin在多种恶性肿瘤中高表达,并且在肿瘤的发生、发展中发挥重要作用,为肿瘤的诊断及治疗提供了新的研究方向.     

凋亡抑制新基因Livin与宫颈癌的关系

凋亡蛋白抑制因子(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,能够与内源IAP抑制剂SMAC和caspase-3、caspase-7、caspase-9结合,发挥抗细胞凋亡的作用.近年来,研究发现Livin在宫颈癌细胞及组织中高表达,而且通过检测癌细胞凋亡有助于确定宫颈癌的发生机制及其疗效评价,因此研究Livin结构与功能及作用机制对于宫颈癌的发生、发展、诊断与治疗有积极意义.     

FHIT和Livin在非小细胞肺癌中的表达及临床意义

目的 检测FHIT和Livin蛋白在非小细胞肺癌组织中的表达,并对其表达水平与NSCLC临床特征之间的关系进行相关性分析,探讨其与NSCLC的浸润、转移的关系及临床意义。方法 采用免疫组织化学SP法检测60例NSCLC组织及19例癌旁正常肺组织中FHIT和Livin蛋白的表达情况,并结合肺癌的临床病理特征进行对比分析。结果 FHIT在NSCLC中的阳性表达率显著低于正常肺组织(P＜0.05),Livin在NSCLC中的阳性表达率显著高于正常肺组织(P＜0.05);FHIT和Livin蛋白表达率均与肺癌的病理类型、细胞分化程度、淋巴结转移、TNM分期密切相关(P＜0.05),而与患者年龄、性别、肿瘤部位及肿块大小无关(P＞0.05);FHIT与Livin蛋白表达两者呈负相关(P＜0.05)。结论 FHIT和Livin蛋白可以作为判断非小细胞肺癌的特异性指标,并为肿瘤基因治疗提供了新的靶点。     

Livin蛋白和血管内皮生长因子在肿瘤中的表达

Livin是抑制凋亡蛋白家族（IAP）的新成员,在多数恶性肿瘤组织中高表达,其主要功能是抑制细胞凋亡。细胞凋亡与肿瘤细胞的发生、发展密切相关,肿瘤的生存更有赖于血管的生成。血管内皮生长因子（VEGF）是目前所知作用最强的一种促血管生长因子,几乎在所有的人体肿瘤和肿瘤细胞株中皆有表达。现就Livin和VEGF在肿瘤中的表达作一综述。     

凋亡抑制新基因Livin与宫颈癌的关系

凋亡蛋白抑制因子(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,能够与内源IAP抑制剂SMAC和caspase-3、caspase-7、caspase-9结合,发挥抗细胞凋亡的作用.近年来,研究发现Livin在宫颈癌细胞及组织中高表达,而且通过检测癌细胞凋亡有助于确定宫颈癌的发生机制及其疗效评价,因此研究Livin结构与功能及作用机制对于宫颈癌的发生、发展、诊断与治疗有积极意义.     

Livin在小细胞肺癌组织中的表达

目的：探讨凋亡抑制蛋白（inhibitor of apoptosis protein,IAP）家族中的新成员Livin在小细胞肺癌（small cell lung cancer,SCLC）组织中的表达及其与临床病理的关系。方法：采用反转录-聚合酶链反应（RT-PCR）技术检测SCLC组织中LivinαmRNA和LivinβmRNA的表达,并用western blot分析Livin蛋白的表达。结果：30例SCLC组织中有19例Livin表达,阳性率为63.33%,其表达与患者年龄、性别、肿瘤的TNM分期、淋巴结转移和肿瘤大小均无关（P〉0.05）。而16例癌旁正常肺组织中Livin低表达,阳性率为12.5%（P〈0.01）。结论：Livin在SCLC组织中异常表达,有望成为小细胞肺癌诊断和基因治疗的新靶点。     

Livin与肿瘤细胞凋亡的研究现状

凋亡蛋白抑制因子(inhibitor of apoptosisprotein,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:Livinα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     

Livin与肿瘤细胞凋亡的研究现状

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     

凋亡抑制蛋白基因Livin及肿瘤转移相关基因在肺癌组织中的表达及其与肺癌临床特征的关系分析

目的 分析凋亡抑制蛋白基因Livin及肿瘤转移相关基因在肺癌组织中的表达及其与肺癌临床特征的关系.方法 选取确诊并治疗的肺癌患者392例,采用逆转录多聚酶链式反应(RT-PCR)检测392例肺癌组织中的Livin、基质细胞衍生因子-1(SDF-1)、趋化因子受体-4(CXCR4)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶9(MMP-9)mRNA的表达水平.同时选取306例肺癌患者癌旁正常肺组织、297例肺部良性病变患者的肺部良性病变组织,采用RT-PCR检测Livin、SDF-1、CXCR4、MMP-2、MMP-9 mRNA的表达水平.结果 肺癌组织中Livin、Livinα、Livinβ、SDF-1、CXCR4、MMP-2、MMP-9的阳性表达率均高于癌旁正常肺组织和肺部良性病变组织(P﹤0.05);肺癌组织中Livinα表达水平为(0.35±0.09),高于Livinβ的(0.28±0.05)(P﹤0.05).结论 肿瘤组织中的Livin、SDF-1、CXCR4、MMP-2、MMP-9表达水平较高,Livinα和化疗有密切关系,Livinβ和肿瘤位置有相关性,MMP-9与肿瘤是否发生转移有密切关系.     

Livin靶向siRNA诱导大肠癌细胞调亡的作用

Objective:To construct siRNA recombinant expression vector targeting Livin gene and observe the apoptosis induction effecl of it in human colon cancer cells.Methods:SiRNA recombinant expression vector targeting Livin gene was constructed and transfected into human colon cancer cell.The effect of siRNA recombinant expression vector was detected by RT-PCR,Westem blot,MTT reduction assay and flow cytometry.Results:It was confirmed by restriction endonuclease and sequence analysis that siRNA recombinant expression vector targeting Livin gene was constructed successfully.Inhibition ratio of Livin siRNA at mRNA and protein levels were 30.18% and 28.88%.The growth of cancer cells was inhibited significantly and the apoptotic ratio was 13.36±1.45%.Conclusion:The siRNA recombinant expression vector targeting Livin gene has been constructed successfully.It not only can inhibit the expression of Livin gene but also can induce apoptosis in human colon cancer cells remarkably.     

凋亡抑制蛋白Livin与肿瘤

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.