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整合素信号转导通路对K562细胞凋亡的影响

Effect of Integrin-mediated Signal Transduction Pathways on Apoptosis of K562 Cells

  • 摘要: 目的 探讨整合素介导的细胞凋亡抑制途径是否参与了慢性粒细胞白血病(CML)急变期细胞株K562细胞的凋亡耐受机制,以求为CML的治疗提供新思路。 方法 流式细胞术和丫啶橙双色荧光显微镜分析检测抗整合素α5β1单抗(Anti-α5β1)对K562细胞凋亡的影响,Western blot 技术和RT-PCR技术分析Anti-α5β1对K562细胞内凋亡相关因子PI3K、AKT和survivin表达的影响。 结果 Anti-α5β1可通过抑制K562细胞内PI3K和survivin mRNA的表达,下调AKT和PI3K蛋白表达水平及蛋白磷酸化水平诱导K562细胞凋亡。抗整合素α5β1抗体的促凋亡能力强于IFNα-2b,其原因可能与IFNα-2b不能显著降低PI3K和p-AKT表达水平有关。 结论 整合素α5β1介导的PI3K-AKT-survivin信号转导通路参与了K562细胞的凋亡耐受。

     

    Abstract: Objective To evaluate the role of integrin mediated signal transduction pathway in the apoptosis of K562 cells. Methods The percentage of apoptotic K562 cells induced by Anti-α5β1 was measured by FCM and acridine orange/ethidium bromide (AO/EB) double fluorescent dye staining, the expression levels of PI3K and survivin mRNA were measured by RT-PCR. The AKT and PI3K protein expression levels and the phosphorylation levels of these proteins were detected by Western blot method. Results Anti-α5β1 antibodies induced apoptosis of K562 cells and down-regulated the expression levels of PI3K mRNA and protein, survivin mRNA and AKT protein. The effect of Anti-α5β1 was much stronger than that of IFNα-2b. Conclusion The PI3K-AKT-survivin signal transduction pathway mediated by integrin α5β1 might contribute to the apoptosis of K562 cells.

     

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