The study on drug reverse effect and reverse mechanism of naringin on multi-drug resistant human ovarian cell line SKOV3/DDP

WANG Lei; CAI Liping

Abstract：Objective To investigate the effect of naringin on the proliferative inhibition of cisplatin ( DDP )-resistant ovarian cancer SKOV3/DDP cells in vitro and its reverse effect of drug resistance, as well as the possible mechanisms. Methods DDP to half maximal inhibitory concentration ( IC50 ) on SKOV3 and SKOV3/DDP cells was determined by MTT method. The proliferatiive inhibi-tion of naringin alone and naringin in combination with DDP on SKOV3/DDP cells was tested by MTT method. Non-cytotoxic naringin was selected, and SKOV3/DDP cells were divided into blank control group, 2. 5μg/ml DDP group, 10μmol/L naringin group and 10μmol/L naringin+2. 5 μg/ml DDP group. RT-PCR and Western blotting was used to detect the MDR1 and MRP2 mRNA levels and protein expressions of P-gp and MRP2. Results After treated with 1-32 μg/ml DDP for 48 h, the IC50 of SKOV3 cells and SKOV3/DDP cells were 5. 48 μg/ml and 14. 93μg/ml, and the resistance index ( RI) was 2. 72. Naringin could effectively restrain the prolif-eration of SKOV3/DDP cells in a time and dose dependent manner. The dose of 10μmol/L naringin was chosen for the further experi-ment. The RI was 1. 62 and the drug resistance reversal fold was 1. 68 times after 10μmol/L naringin+2. 5μg/ml DDP acted on SK-OV3/DDP cells. The mRNA levels of MDR1 and MRP2, as well as the protein expressions of P-gp and MRP2 decreased significantly in 10 μmol/L naringin+2. 5 μg/ml DDP group compared with 2. 5 μg/ml DDP group ( P<0. 05) . Conclusion Naringin can signifi-cantly inhibit the proliferation of SKOV3/DDP cells in vitro, and can enhance the sensitivity of SKOV3/DDP cell to DDP. The reversal mechanism of drug resistance may be related to the inhibition of MDR1 and MRP2 mRNA and related proteins.