Enhanced chemosensitivity of cholangiocarcinoma cell line QBC939 to gemcitabine induced by curcumin

Abstract

Objective To investigate the effect of curcumin in enhancing chemosensitivity of cholangiocarcinoma cell line QBC939 to gemcitabine and its mechanism. Methods QBC939 cells were divided into control group, 5 μmol/L curcumin group, 0.625 μg/ml gemcitabine group and 5 μmol/L curcumin combined 0.625 μg/ml gemcitabine group. Methyl thiazol tetrazolium (MTT) assay was used to detect the proliferation inhibition effect, flow cytometry was used to detected the change of cell cycle and apoptosis rate. Expressions of nuclear factor-κB (NF-κB), Cyclin B1 and inhibitor of apoptosis proteins (IAP)-1 in different groups were detected by Western blotting. Results Compared with control group, curcumin group and gemcitabine group, the inhibitory rates of cells in curcumin combined gemcitabine group at 12, 24, 48 and 72 h were (10.00±0.02)%, (23.10±0.03)%, (33.23±0.01)%, (48.30±0.05)% respectively, which were significantly higher than those of control group and single medicaments treatment group (P=0.001, 0.000, 0.000, 0.000); besides, curcumin combined with gemcitabine blocked (28.75±3.23)% human cholangiocarcinoma cell line QBC939 in G2/M phase, which was significantly higher than those of curcumin group and gemcitabine group [(14.49±2.20)%, (11.82±2.10)%; P=0.000], the apoptosis rate in combined group was (13.64±3.40)%, significantly higher than those of control group, curcumin group and gemcitabine group [(4.53±0.56)%, (6.47±0.98)%, (9.87±1.12)%; P=0.000]; moreover, the relative expression levels of NF-κB and its downstream moleculor Cyclin B1 and IAP-1 proteins in curcumin combined with gemcitabine group were 0.300±0.001, 0.407±0.036, 0.475±0.032 respectively, significantly lower than those of control group, curcumin group and gemcitabine group (P=0.000, 0.001, 0.003). Conclusion Curcumin can enhance the sensitivity of human cholangiocarcinoma cell line QBC939 to gemcitabine through the inactivation of NF-κB signaling pathway. Key words: Cholangiocarcinoma cell; Curcumin; Gemcitabine; Cholangiocarcinoma cell line QBC939; Nuclear factor-κB