关键词: 硼替佐米, 力达霉素, 多发性骨髓瘤, 联合用药, 内质网应激

Abstract:

Objective To investigate the effect of lidamycin (LDM) combined with bortezomid (BZM) against multiple myeloma and the mechanism of the combination treatment.

Methods The human multiple myeloma SKO-007 cells in logarithm growth phase were selected and  randomly divided into control group,LDM group,BZM group,and BZM combined with LDM group. MTS assay was used to detect the survival  rate of SKO-007 cells and  flow cytometry  was used to analyze
the distribution of cell cycle and  apoptotic rate of the proliferation cells in various groups;the expression levels of protein associated with apoptosis and endoplasmic reticulum stress (ERS) of SKO-007 cells in various groups were detected by Western blotting method.
Results After  culture for 48 h,the survival  rate of the  cells  in BZM combined with LDM group was lower than
those  in control,LDM and BZM groups (P<0.05). The percentage of cells at  G₂/M phase, the  apoptotic rate  of cells,
 the expression levels  of cleaved caspase-3 and poly ADP-ribose polymerase (PARP) of SKO-007 cells,the expressio
n levels  of GRP78/Bip,CHOP/GADDl53,and phosphorylation of c-Jun NH2-terminal kinase (p-JNK
) in BZM combined with LDM group were higher than those in control,LDM and BZM
 groups (all P<0.05). Conclusion BZM can greatly enhance the efficacy of LDM against
multiple myeloma by increasing the levels of cleaved caspase-3 and PARP,and remarkably increase the apoptosis induced by LDM through further activation of ERS.

Key words: bortezomid, lidamycin, multiple myeloma, combination therapy, endoplasmic reticulum stress