Abstract:

Objective  To investigate the effect of lidamycin (LDM) on signal transmission pathway of  mitogen-activated protein kinases (MAPKs) in mouse myeloma  cells and the role of  MAPKs in cell growth and apoptosis induced by LDM,and to provide basis  for research on treatment of  human multiple myeloma with LDM.Methods The mouse myeloma SP2/0 cells in logarithm growth phase were selected and  randomly divided into blank control group and four different concentrations of LDM groups.The expression levels of c-Jun amino-terminal kinase(JNK),extracellular signal-regulated kinase(ERK) and p38 MAPK were detected 48 h after  culture by Western blotting.And then the SP2/0 cells in logarithm growth phase were selected and randomly divided into  control group,LDM group,SP600125 (JNK inhibitor) group, SB203580 (p38 inhibitor)group,U0126 group(ERK inhibitor),LDM +SP600125 group,LDM + SB203580 group,and LDM + U0126 group.MTS assay was used to detect SP2/0 cell proliferation and flow cytometry was used to analyze  apoptosis in various groups.Results The expression levels of JNK,ERK and p38 MAPK in SP2/0 cells in different concentrations of  LDM groups were higher than those in blank control group (P<0.05) 48 h after culture; Compared with blank control group,the apoptotic rates and proliferation rates in different inhibitors groups had no significant differences(P>0.05),in  other words,the proliferation inhibition and apoptosis induction in  SP600125 group, SB203580 group,and U0126 group were not obvious.The effects of LDM on the growth inhibition and apoptosis of cells were decreased in LDM +SP600125 group and LDM + SB203580 group  (P<0.05)and increased in LDM + U0126 group (P<0.05).Conclusion LDM can inhibit the proliferation of mouse  myeloma  SP2/0 cells and induce apoptosisthrough  activation of JNK and p38 MAPK.

Key words: lidamycin;apoptosis;myeloma;mitogen-activated protein kinases