[Reversal of multidrug resistance of the drug resistant human multiple myeloma cell line MOLP-2/R by curcumin and its relation with FA/BRCA pathway].
OBJECTIVE
To investigate the reverse effect of mutidrug resistance of curcumin combined with melphalan on the mutidrug-resistant human multiple myeloma cell line MOLP-2/R and the relation with FA/BRCA pathway.


METHODS
The inhibitory effects of the drugs on the growth of MOLP-2/R cells were determined by MTT assay. Cell cycle analysis, intracellular drug concentration and apoptosis were assayed by flow cytometry. The expression of FANCD2 monoubiquitination was determined by Western blot analysis.


RESULTS
Co-administration of curcumin and melphalan had an synergistic inhibitory effects on the proliferation, IC50 of melphalan with 10 micromol/L curcumin reduced from 45.5 micromol/L to 19 micromol/L in MOLP-2/R cells. The apoptosis percentage of MOLP-2/R cells was significantly increased from (23.3 +/- 0.6)% to (52.6% +/- 0.8)% by the treatment of melphalan 20 micromol/L plus curcumin 10 micromol/L with the increased percentage of cells in the G2/M phase (from 9.1% to 18.5%) and enhanced intracellular drug concentration of MOLP-2/ R cells (from 15.2 +/- 0.3 to 21.4 +/- 0.8 ). The effects were accompanied with inhibition of FA/BRCA pathway by down regulation of FANCD2 protein monoubiquitination.


CONCLUSIONS
Curcumin combined with melphalan results in synergistic effects and reverses multiple drug resistance of MOLP-2/R cells effectively. The inhibition of FA/BRCA pathway may be the mechanism.
Xiao
Hui
H
Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Zhang
Ke-Jian
KJ
Zuo
Xue-Lan
XL
D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000378:metabolism; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*
C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; D003474:Curcumin