Abstract
The aim of this study was to investigate the antiproliferative effect of curcumin combined with cyclophosmide on the growth of human lymphoma cell line HT/CTX with drug resistance and its relation with FA/BRCA pathway. The inhibitory effects of the drugs on the growth of HT/CTX cells were determined by MTT assay. Cell cycle phase and apoptosis were analyzed by flow cytometry. The expression of FANCD2 protein in FA/BRCA pathway was determined by Western blot. The results indicated that the combination of curcumin with CTX had an additional synergistic inhibitory effects on the proliferation and cell cycle distribution of HT/CTX cells. The curcumin could enhance toxicity of CTX on HT/CTX cells through inhibition of FA/BRCA pathway which was realized by suppression of FANCD2 monoubiquitination. The curcumin combined with CTX could increase apoptosis inducing effect on HT/CTX cells, while the curcumin or CTX alone did not showed this effect, and without inhibition of FA/BRCA pahtway. It is concluded that combination of curcumin and CTX produces synergistic effects and reverses multiple drug resistance of HT/CTX cells effectively. The prevention of cells from entering the next cell cycle and down regulation of FANCD2 protein monoubiquitination may be involved in the mechanism.
