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首页> 外文期刊>Cellular Physiology and Biochemistry >CYC1 Silencing Sensitizes Osteosarcoma Cells to TRAIL-Induced Apoptosis
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CYC1 Silencing Sensitizes Osteosarcoma Cells to TRAIL-Induced Apoptosis

机译：CYC1沉默诱导骨肉瘤细胞TRAIL诱导的细胞凋亡。

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biAims /i/bOsteosarcoma (OS) is an aggressive bone malignancy with poor prognosis. Many OS cells are resistant to apoptotic induction by tumor necrosis factor-related apoptosis inducing ligand (TRAIL). In our previous study, we found that the serum level of cytochrome c1 (CYC1) is significantly higher in OS patients than in healthy subjects. Our aim was to investigate the effects of CYC1 silencing on TRAIL-induced apoptosis in human OS in ivitro/i and iin vivo/i along with the underlying mechanisms. biMethods /i/bFirst, we determined the expression of CYC1 in human OS tumors and cell lines versus normal adjacent tissues and cell line. We then studied the effects of CYC1 silencing alone or in combination with TRAIL on OS cell growth and apoptosis iin vitro/i and OS tumorigenesis iin vivo/i. biResults /i/bWe found that CYC1 is overexpressed in human OS tissues and cell lines. CYC1 silencing by shRNA transfection inhibits proliferation, slightly induces apoptosis in human OS cells iin vitro/i, and suppresses human OS tumor growth in a mouse xenograft model iin vivo/i. Additionally, CYC1 silencing sensitizes OS to TRAIL-induced apoptosis iin vitro/i and iin vivo/i. Our results also showed that CYC1 silencing significantly reduces complex III activity and potentiates TRAIL-induced cytochrome c release and caspase-9 activation in OS cells, suggesting that CYC1 silencing acts via the mitochondria-dependent apoptotic pathway. biConclusion /i/bTaken together, our results provide evidence that CYC1 plays an important role in OS tumorigenesis, and modulation of CYC1 may be an effective strategy to potentiate OS to apoptotic induction by TRAIL.
机译：目标 骨肉瘤（OS）是一种侵袭性骨恶性肿瘤，预后不良。许多OS细胞对肿瘤坏死因子相关的凋亡诱导配体（TRAIL）的凋亡诱导具有抗性。在我们先前的研究中，我们发现OS患者的细胞色素c1（CYC1）血清水平明显高于健康受试者。我们的目的是研究CYC1沉默对TRAIL诱导的体外和体内人OS中细胞凋亡的作用及其潜在机制。 方法 首先，我们确定CYC1在人OS肿瘤和细胞系中与正常相邻组织和细胞系中的表达。然后，我们研究了CYC1沉默单独或与TRAIL联合对体外OS细胞生长和凋亡以及体内OS肿瘤发生的影响。 结果 我们发现CYC1在人类OS组织和细胞系中过表达。通过shRNA转染使CYC1沉默在体外小鼠体内异种移植模型中抑制增殖，在人OS细胞中略微诱导细胞凋亡，并抑制人OS肿瘤的生长。此外，CYC1沉默可使OS对TRAIL诱导的细胞凋亡体外和体内。我们的结果还表明，CYC1沉默可显着降低复合物III的活性，并增强OS细胞中TRAIL诱导的细胞色素c释放和caspase-9激活，表明CYC1沉默可通过线粒体依赖性凋亡途径发挥作用。 结论 总之，我们的结果提供了证据，表明CYC1在OS肿瘤发生中起重要作用，而CYC1的调节可能是增强OS诱导TRAIL诱导细胞凋亡的有效策略。

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