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首页> 外文期刊>Spine >Blockage of Stat3 With CDDO-Me Inhibits Tumor Cell Growth in Chordoma.
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Blockage of Stat3 With CDDO-Me Inhibits Tumor Cell Growth in Chordoma.

机译:用CDDO-Me阻断Stat3可抑制脊索瘤中肿瘤细胞的生长。

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STUDY DESIGN.: An experimental study to investigate the activation of Src/Stat3 pathways in chordomas and blockage of this pathway as a potential strategy for chordoma treatment. OBJECTIVE.: To investigate the activation of Src/Stat3 pathway in chordomas cells and to determine the efficiency of inhibiting this pathway by 2-cyano-3,12-dioxooleana-1,9 (11)-dien-28-oic acid-methyl ester (CDDO-Me) as a potential chemotherapeutic agent for chordoma treatment. SUMMARY OF BACKGROUND DATA.: The advent of molecularly targeted therapies has raised interest for their use in the treatment of chordomas. Unfortunately, the current understanding of molecular markers in chordomas is limited. Constitutive activation of Stat3 is a common finding in a wide spectrum of human cancers. The function of Stat3 pathway in chordomas has not been elucidated. METHODS.: The expression of key components of the Src/Stat3 signaling cascade was evaluated by Western blot in chordoma tissues and chordoma cell lines. The effects of CDDO-Me on chordoma cell growth were evaluated in these chordoma cell lines by MTT assay. The expression of key components of the Src/Stat3 signaling cascade and poly (ADP-ribose) polymerase cleavage in these CDDO-Me treated cells were analyzed by Western blot and immunofluorescence. Furthermore, the synergistic effect of CDDO-Me on cisplatin and doxorubicin-induced cytotoxicity was evaluated by MTT. Finally, chordoma cells were grown in a 3-dimensional (3D) culture and treated with CDDO-Me. RESULTS.: The key components of the Src/Stat3 signaling cascade, including Stat3, pStat3, Src, pSrc, Bcl-xL, and Myeloid Cell Leukemia-1, were all highly expressed in chordomas. Expression of the key components of the Src/Stat3 signaling cascade was inhibited in chordoma cells after treatment with CDDO-Me. The growth of chordoma cells was inhibited and apoptosis associated poly (ADP-ribose) polymerase cleavage was detected after treatment with CDDO-Me. Additionally, CDDO-Me has a synergistic effect on cisplatin or doxorubicin-induced chordoma cell death (P < 0.001). Finally, expression of pSrc and pStat3 and chordoma cell growth was inhibited by treatment of CDDO-Me using 3D culture. CONCLUSION.: The Src/Stat3 signaling pathway was activated in chordomas. Blockage of Src/Stat3 pathway by CDDO-Me is a potential strategy for chordoma treatment and may be focus for future research.
机译:研究设计:一项实验性研究,旨在研究脊索瘤中Src / Stat3途径的激活以及该途径的阻断,作为脊索瘤治疗的潜在策略。目的:研究脊索瘤细胞中Src / Stat3途径的激活,并确定2-氰基-3,12-二氧代油菜-1,9(11)-dien-28-oic酸-甲基对这种途径的抑制作用酯(CDDO-Me)作为脊索瘤治疗的潜在化学治疗剂。背景技术概述:分子靶向疗法的出现引起了人们对脊索瘤治疗的兴趣。不幸的是,目前对脊索瘤中分子标志物的理解是有限的。 Stat3的组成性激活是广泛的人类癌症中的常见发现。 Stat3途径在脊索瘤中的功能尚未阐明。方法:通过Western blot评估脊索瘤组织和脊索瘤细胞系中Src / Stat3信号级联反应关键成分的表达。通过MTT分析在这些脊索瘤细胞系中评估了CDDO-Me对脊索瘤细胞生长的影响。通过蛋白质印迹和免疫荧光分析了这些CDDO-Me处理的细胞中Src / Stat3信号级联和聚(ADP-核糖)聚合酶裂解的关键成分的表达。此外,通过MTT评估了CDDO-Me对顺铂和阿霉素诱导的细胞毒性的协同作用。最后,脊索瘤细胞在3维(3D)培养中生长并用CDDO-Me处理。结果:Src / Stat3信号级联的关键组件,包括Stat3,pStat3,Src,pSrc,Bcl-xL和Myeloid Cell Leukemia-1,都在脊索瘤中高表达。用CDDO-Me处理后,脊索瘤细胞中Src / Stat3信号级联反应关键成分的表达受到抑制。用CDDO-Me处理后,脊索瘤细胞的生长受到抑制,并检测到凋亡相关的聚(ADP-核糖)聚合酶裂解。另外,CDDO-Me对顺铂或阿霉素诱导的脊索瘤细胞死亡具有协同作用(P <0.001)。最后,通过使用3D培养物处理CDDO-Me,可抑制pSrc和pStat3的表达以及脊索瘤细胞的生长。结论:脊索瘤中Src / Stat3信号通路被激活。 CDDO-Me阻断Src / Stat3途径是脊索瘤治疗的一种潜在策略,可能是未来研究的重点。

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