Chinese Clinical Oncology

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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.   

  1. Department of Gynecology and Obstetrics, the First Affiliated Hospital of Nanchang University
  • Received:2016-04-27 Revised:2016-06-13 Online:2016-07-30 Published:2016-07-30
  • Contact: 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. MethodsDDP to half maximal inhibitory concentration (IC50) on SKOV3 and SKOV3/DDP cells was determined by MTT method. The proliferatiive inhibition 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, 2.5 μg/ml DDP group, 10 μmol/L naringin group and 10 μmol/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. ResultsAfter 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 14.93 μg/ml, and the resistance index (RI) was 2. 72. Naringin could effectively restrain the proliferation of SKOV3/DDP cells in a time and dose dependent manner. The dose of 10 μmol/L naringin was chosen for the further experiment. The RI was 1.62 and the drug resistance reversal fold was 1.68 times after 10 μmol/L naringin+2.5 μg/ml DDP acted on SKOV3/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). ConclusionNaringin can significantly 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.

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