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背景和目的:IL-6能够抑制多种因素诱发的骨髓瘤细胞凋亡反应,在此过程中涉及到胞浆内一系列信号蛋白分子的参与。本研究旨在确定能够介导IL-6在人骨髓瘤细胞系XG-7上凋亡抑制效应的Bcl-2家族抗凋亡蛋白(Bcl-2,Bcl-xL,Mcl-1)和IL-6信号转导途径(JAK/STAT、Ras/MAPK、PI-3K/Akt途径)。方法:采用碘化丙腚(PI)染色和流式细胞术分析XG-7细胞的凋亡情况;采用免疫印迹方法检测Bcl-2家族分子在XG-7细胞中的表达情况;分别采用针对JAK/STAT、Ras/MAPK和PI-3K/Akt途径的特异性抑制剂AG490、PD98059和LY294002处理XG-7细胞,从而确定哪条信号转导途径能够介导IL-6在XG-7细胞上的凋亡抑制效应。结果:IL-6能够抑制XG-7细胞凋亡,同时上调Bcl-2家族抗凋亡蛋白Mcl-1表达。AG490处理的XG-7细胞中Mcl-1表达上调被明显抑制;但PD98059和LY294002处理后对Mcl-1表达没有显著影响。结论:IL-6在XG-7细胞上的凋亡抑制效应是通过上调Mcl-1表达和激活JAK/STAT途径而介导的,与Ras/MAPK和PI-3K/Akt途径的活化状态无关。
BACKGROUND & AIM: IL-6 inhibits myeloma cell apoptosis induced by various factors, involving the involvement of a series of signaling proteins in the cytoplasm. This study aimed to identify Bcl-2 family anti-apoptotic proteins (Bcl-2, Bcl-xL, Mcl-1) and IL-6 that could mediate the inhibitory effect of IL-6 on human myeloma cell line XG- 6 signal transduction pathway (JAK / STAT, Ras / MAPK, PI-3K / Akt pathway). Methods: The apoptosis of XG-7 cells was analyzed by propidium iodide (PI) staining and flow cytometry. Western Blot was used to detect the expression of Bcl-2 family members in XG-7 cells. XG-7 cells were treated with the specific inhibitors AG490, PD98059 and LY294002 in order to determine which signal transduction pathway could mediate the effect of IL-6 on XG-7 cells Apoptosis inhibitory effect. Results: IL-6 could inhibit the apoptosis of XG-7 cells and up-regulate the expression of Mcl-1, an anti-apoptotic protein of Bcl-2 family. The up-regulation of Mcl-1 expression was significantly inhibited in AG490-treated XG-7 cells; however, PD98059 and LY294002 had no significant effect on Mcl-1 expression. CONCLUSION: The inhibitory effect of IL-6 on XG-7 cells is mediated through the up-regulation of Mcl-1 expression and activation of JAK / STAT pathway, but not with the activation of Ras / MAPK and PI-3K / Akt pathway.