Objective: To investigate the reversal effect of hyperin on vincristine (VCR)-resistant colon cancer HCT8/VCR cells

and its possible mechanism. Method: HCT8 cells and HCT8/VCR cells were cultured with hyperin at the concentrations of 2.5-80 mg·L-1 and vincristine at concentrations of 1.25-40 mg·L-1. The inhibitory rate of the cell growth was measured by Methylthiazolyldiphenyl-tetrazolium bromide(MTT) assay. The 50% inhibitory concentration (IC50) of hyperin and vincristine

as well as non-cytotoxic dose of hyperin were counted. HCT8/VCR cells were treated with hyperin at non-cytotoxic dose with different concentrations of vincristine (VCR

1.25-40 mg·L-1) to determine IC50 and the reversal multiple in all groups. The apoptotic rate and the changes in mitochondrial membrane potential were evaluated by flow cytometry. The activities of Caspase-3 and Caspase-9 were detected by colorimetric assays. Result: Hyperin at the concentration of 0.82 mg·L-1 has no significant cytotoxicity to HCT8/VCR cells. Hyperin at the concentration of 0.82 mg·L-1 decreased the IC50 value of vincristine to HCT8/VCR cells from 65.97 mg·L-1 to 9.94 mg·L-1

with the reversal multiple of 6.63.The apoptotic rate and Caspase-3 and Caspase-9 activities in combination group were significantly increased compared with vincristine group(P<0.01). The data of mitochondrial membrane potential showed that the percentage of cells in low fluorescence in combination group was increased compared with vincristine group (P<0.01). Conclusion: Vincristine combined with hyperin could increase Caspase-3 and Caspase-9 protein activities

decrease the mitochondrial membrane potential

and enhance apoptosis rate

so as to reverse the multidrug resistance of HCT8/VCR cells.