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首页> 外文期刊>Journal of Cellular Physiology >PI-3K/Akt and NF-kappaB/IkappaBalpha pathways are activated in Jurkat T cells in response to TRAIL treatment.
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PI-3K/Akt and NF-kappaB/IkappaBalpha pathways are activated in Jurkat T cells in response to TRAIL treatment.

机译:PI-3K / Akt和NF-kappaB / IkappaBalpha通路激活Jurkat T细胞的反应治疗。

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The aim of this work was to evaluate the involvement of survival pathways in the response of Jurkat T leukaemic cells sensitive to the cytotoxic action of tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)/Apo2L. Jurkat T cells express TRAIL-R2/DR5 and TRAIL-R4/DcR2 receptors and start to die by apoptosis early (3 h) upon TRAIL administration reaching a dose-dependent increase in the percentage of dead cells within 48 h (up to 85-90%). This increase in cell death is accompanied by a dose-dependent significant (P < 0.05) increase in the G0/G1 phase of the cell cycle and reverted by the treatment with a broad inhibitor of caspases, z-VAD-fmk. Co-treatment of the cells with inhibitors of PI-3 kinase (LY294002) and nuclear factor kappa B (NF-kappaB) (SN50) pathways leads to an earlier significantly increased cytotoxicity, respectively in the form of apoptosis and necrosis. Consistently with the data obtained with the pharmacological inhibitors, the activation and nuclear translocation of both PI-3K and NF-kappaB were observed. In summary, our results provide evidence that even in sensitive neoplastic cells TRAIL paradoxically activates pro-survival pathways, which protect against TRAIL-mediated death since their inhibition leads to an earlier and increased cytotoxicity.
机译:这项工作的目的是评估在响应中参与的生存途径Jurkat T进展期细胞敏感肿瘤坏死因子的细胞毒性作用肿瘤坏死因子相关凋亡诱导配体(小路)/ Apo2L。TRAIL-R2 / DR5和TRAIL-R4 / DcR2受体开始死亡,细胞凋亡早期(3 h)在小道政府增加存在剂量依赖的相关性死细胞的百分比在48 h (85 - 90%)。伴随着显著存在剂量依赖的相关性(P <0.05)增加在G0 / G1期细胞广泛的治疗周期和恢复还存在的抑制剂,z-VAD-fmk。细胞PI-3激酶的抑制剂(LY294002)和核转录因子k B (NF-kappaB)(SN50)途径导致早期显著增加细胞毒性,分别在表单中细胞凋亡和坏死。与药理数据获得抑制剂,激活和核易位PI-3K和NF-kappaB观察到。证据表明,即使是在敏感的肿瘤细胞小道矛盾激活pro-survival通路,防止TRAIL-mediated因为他们的抑制导致早期死亡和细胞毒性增加。

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