CAJ | 학술논문

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.
배경화목적:IL-6능구억제다충인소유발적골수류세포조망반응,재차과정중섭급도포장내일계렬신호단백분자적삼여.본연구지재학정능구개도IL-6재인골수류세포계XG-7상조망억제효응적Bcl-2가족항조망단백(Bcl-2,Bcl-xL,Mcl-1)화IL-6신호전도도경(JAK/STAT、Ras/MAPK、PI-3K/Akt도경).방법:채용전화병정(PI)염색화류식세포술분석XG-7세포적조망정황;채용면역인적방법검측Bcl-2가족분자재XG-7세포중적표체정황;분별채용침대JAK/STAT、Ras/MAPK화PI-3K/Akt도경적특이성억제제AG490、PD98059화LY294002처리XG-7세포,종이학정나조신호전도도경능구개도IL-6재XG-7세포상적조망억제효응.결과:IL-6능구억제XG-7세포조망,동시상조Bcl-2가족항조망단백Mcl-1표체.AG490처리적XG-7세포중Mcl-1표체상조피명현억제;단PD98059화LY294002처리후대Mcl-1표체몰유현저영향.결론:IL-6재XG-7세포상적조망억제효응시통과상조Mcl-1표체화격활JAK/STAT도경이개도적,여Ras/MAPK화PI-3K/Akt도경적활화상태무관.
Background ＆ Objective： IL- 6 can protect myeloma cells from apoptosis induced by various stimuli. A series of intracellular molecules might participate in this process. Our aim in this study is to investigate which anti- apoptotic Bcl- 2 family proteins (Bcl- 2,Bcl- Xl,Mcl- 1) and which signal transduction pathway（ JAK/STAT， Ras/MAPK,PI- 3K/Akt） can mediate the anti- apoptotic effect of IL- 6 on a human myeloma cell line XG- 7. Methods: Apoptosis of XG- 7 cells was analyzed by flow cytometry with propidium iodide(PI) staining of nuclei. The expression of three Bcl- 2 family proteins in XG- 7 cells were monitored by immunoblot assay.AG490,PD98059,and LY294002,three specific antagonists for JAK/STAT, Ras/MAPK, and PI- 3K/Akt signal transduction pathways respectively, were used to determine which signal transduction pathway was responsible for the effect of IL- 6 on XG- 7 cells. Results:IL- 6 inhibited the apoptosis of XG- 7 cells and up- regulated the expression of only one of the three anti- apoptotic Bcl- 2 family proteins- Mcl- 1.In addition, up- regulation of Mcl- 1 expression induced by IL- 6 was significantly inhibited in the presence of AG490,while not of PD98059 and LY294002. Conclusions:IL- 6 inhibited apoptosis of XG- 7 cells through up- regulation of Mcl- 1 and the activation of JAK/STAT rather than Ras/MAPK nor PI- 3K/Akt signal transduction pathway.