多发性骨髓瘤中MAPK信号通路对BLyS表达的调控研究

The regulation of BLyS expression levels through MAPK signal pathway in multiple myeloma

目的 研究多发性骨髓瘤（MM）细胞中丝裂原活化蛋白激酶（MAPK）信号通路的表达及活化情况,探讨MAPK信号通路对MM细胞B淋巴细胞刺激因子（BLyS）表达变化的影响及对MM细胞增殖与存活的影响,并初步探讨MAPK信号通路在IFN-γ（MM重要的促生长因子）上调MM细胞BLyS表达过程中的作用.方法 应用Western blot方法检测MM细胞中蛋白ERK、p-ERK、JNK、p-JNK、p38及p-p38的表达情况；应用RT-PCR及Western blot检测MAPK信号通路对BLyS表达的影响；应用WST-1法检测靶向JNK的MAPK信号通路抑制剂SP600125对MM细胞增殖与存活的影响.结果 MM细胞株中,除了ERK、JNK及p38的表达外,还有活化蛋白p-JNK的表达；靶向JNK的MAPK信号通路抑制剂SP600125可下调MM细胞BLyS的表达,其激动剂茴香霉素（anisomycin）可上调BLyS的表达；IFN-γ可上调MM细胞BLyS的表达,SP600125可部分抵消IFN-γ对BLyS的上调作用；SP600125可抑制MM细胞的增殖与存活.结论 MM细胞中有JNK/SAPK信号通路的活化；JNK/SAPK信号通路的活化程度与BLyS的表达高低呈正相关；JNK/SAPK信号通路在IFN-γ上调MM细胞BLyS表达过程中发挥重要作用.

Objective To investigate the activation of MAPK signal pathway in multiple myeloma and the regulation of BLyS expression levels through MAPK signal pathway; preliminarily study the role of MAPK signal pathway in the up-regulation of BLyS expression levels induced by IFN-γ.Methods Activated MAPK pathway were detected by Western blot,while the expression of BLyS were detected with RT-PCR and Western blot,and Western blot investigated the effect of MAPK pathway on BLyS expression levels induced by IFN-γ.Results In addition to the expression of ERK,JNK,p38,p-JNK was also expressed in MM cell lines,the MAPK pathway inhibitor targeting JNK SP600125 can down-regulate the expression of BLyS,and its activator anisomycin can up-regulate the expression of BLyS.SP600125 restrained the proliferation and survival of MM cells.Conclusion JNK/SAPK pathway was activated in MM cells; The activated degree of JNK/SAPK pathway and the expression level of BLyS was positively correlated.JNK/SAPK pathway play an important role in the up-regulation of BLyS expression levels induced by IFN-γ.