| Objective:To investigate the reversal effects of lopinavir on the multidrug resistance of LLC/ cMOAT cells。Methods:The sensitivity of LLC/ CMV and LLC/ cMOAT cells to the several chemotherapeutics and the cytoactive of LLC/ CMV and LLC/ cMOAT cells treated with different concentrations of lopinavir was determined with MTT assay.The inhibition rate of ADM,VCR,CTX and DDP without and with different concentration of lopinavir to LLC/ CMV and LLC/ cMOAT cells were evaluated with MTT assay. The IC50 of different agents was counted. The LLC/ CMV and LLC/ cMOAT cells intracellular concentration of ADM without and with Lopinavir was detected by flow cytometer ( FCM) , The expressions of MRP2 were detected by FCM.Result:LLC/ cMOAT cells were resistant to ADM,VCR and DDP to a certain extent but not resistant to CTX.At 10μmol/ L and below, lopinavir was not significantly cytotoxic to LLC/ CMV and LLC/cMOAT cells.After the treatment with 2.5μmol/L lopinavir, the chemosensitivities of LLC/ cMOAT cells to VCR and DDP were enhanced, being much higher when treated with 5.0μmol/L of lopinavir. When treated with 2.5 and 5.0μmol/L lopinavir, ADM accumulation in LLC/cMOAT cells were enhanced significantly with the increase of lopinavir concentration in a concentration-depend manner .Cellular cycle analysis demonstrated that0,4,8,16 hours after co-cultured with lopinavir the amount of cells at G0/G1 phase increased from (42.65±3.75)% at 0h to (70.25±5.12)% at 16h.(p<0.05) ; The cell apoptosis rate was enhanced in a time-and concentration-dependent manner with lopinavir when treated at 2.5 and 5.0μmol/L. Conclusion:Lopinavir has reverse effects on the multidrug resistance in LLC/ cMOAT cells, and the reverse effect correlates to lopinavir concentration. The possible mechanism may involve the growth arrest at G1, increase of intracellular drug concentration and promoting apoptosis. The cell apoptosis rate was enhanced in a time-and concentration-dependent manner with lopinavir...
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