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Suppression of Livin Gene Expression by siRNA Leads to Growth Inhibition and Apoptosis Induction in Human Bladder Cancer T24 Cells

机译:siRNA对Livin基因表达的抑制导致人膀胱癌T24细胞的生长抑制和凋亡诱导

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Apoptosis deficiency is a hallmark of many cancer cells. Functional suppression of specific antiapoptotic factors might provide a feasible strategy in cancer gene therapy. Livin, the latest found inhibitor of apoptosis protein (IAP) family member, plays important role in cell growth and apoptosis. It has been reported that Livin is highly expressed in bladder cancer tissues. In this study, we found that, unlike other cancer cell lines, there was only Livin-α not Livin-β expression in bladder cancer cell lines. We further investigated the effects of Livin knockdown on human bladder cancer T24 cell growth and apoptosis. We found that small interfering RNA (siRNA) mediated Livin suppression significantly inhibited T24 cell proliferation and colony formation ability. Livin knockdown dramatically increased the T24 cell apoptotic rate in response to different proa-poptotic stimuli, such as Mitomycin and TNF-alpha, and this was associated with caspase-3 and caspase-9 activation. These results suggest that Livin knockdown can inhibit cell growth and increase sensitivity to apoptotic stimuli, and might serve as a potent target in bladder cancer gene therapy.
机译:细胞凋亡不足是许多癌细胞的标志。特定抗凋亡因子的功能抑制可能在癌症基因治疗中提供可行的策略。 Livin是最新发现的凋亡蛋白(IAP)家族抑制剂,在细胞生长和凋亡中起着重要作用。据报道,Livin在膀胱癌组织中高表达。在这项研究中,我们发现,与其他癌细胞系不同,膀胱癌细胞系中只有Livin-α表达,而没有Livin-β表达。我们进一步研究了敲除Livin对人膀胱癌T24细胞生长和凋亡的影响。我们发现小干扰RNA(siRNA)介导的Livin抑制显着抑制T24细胞增殖和集落形成能力。 Livin敲低极大地提高了T24细胞的凋亡率,以响应不同的原凋亡刺激物,如丝裂霉素和TNF-α,这与caspase-3和caspase-9活化有关。这些结果表明,Livin敲低可以抑制细胞生长并增加对凋亡刺激的敏感性,并可能成为膀胱癌基因治疗的有效靶标。

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