反义核酸抑制人骨髓瘤细胞中的IL-6信号转导功能研究

Antagonism Function of Anti-Sense Nucleic Acids on IL-6 Signal Transduction in Myeloma Cells

目的：研究人骨髓瘤细胞的ＩＬ－６信号转导通路中哪一个环节可作为“ＩＬ－６功能拮抗剂”设计的目标靶位。方法：首先通过凝胶阻滞电泳（ｅｌｅｃｔｒｏｐｈｏｒｅｔｉｃ ｍｏｂｉｌｉｔｙ ｓｈｉｆｔ ａｓｓａｙ，ＥＭＳＡ）、免疫沉淀方法观察人骨髓瘤细胞Ｓｋｏ－００７中参与ＩＬ－６信号转导功能的转录因子－ＳＹＡＴ３，ＮＦ－ＩＬ－６和蛋白做酶ＥＲＫ的诱导活化情况，继而构建和设计了针对这些信号分子的反义表达质粒和反义寡核苷酸，用同样方法观察反义核酸对ＩＬ－６信号转导功能的影响。结果：这些反义核酸可以不同程度地抑制ＩＬ－６在Ｓｋｏ－００７细胞中的信号转导功能。结论：可通过进一步实验确定转录因子、蛋白激酶作为“胞内拮抗剂”作用目标靶位的可行性。

Objective: To investigate which step of IL-6 signal transduction pathways in myeloma cells can be taken as the acting target of the antagonists for IL-6. Methods: EMSA and immunoprecipitation were used to detect the activation of transcription factors(TFs)-STAT3, NF-IL-6 and protein kinase ERK in a myeloma cell line-Sko-007 by IL-6. then anti-sense expression plasmids and anti-sense ODN for these signal moleculars were constructed and designed,the effects of these anti-sense nucleic acids on IL-6 signal transduction in Sko-007 cells were analyzed by the same methods. Results: IL-6 signal transduction could be antagonized by these anti-sense nucleic acids at different extent.Conclusion: TFs or protein kinases in IL-6 signal trareduction pathways can be taken as the target for antagonists design.