Psoralen Reverses Multidrug Resistance Of Hunam Breast Cancer MCF-7/ADR Cells By Modulating The Function Of P-glycoprotein

OBJECTIVE: Acquired and intrinsic multidrug resistance (MDR) is the major reason for the failure of anticancer chemotherapy. The most important component of clinical multidrug resistance is mediated by P-glycoprotein (P-gp), an ABC transporter encoded by the MDR1 gene. There we intend to study the impact of psoralen on P-gp mediated MDR in human breast cancer MCF-7/ADR cells.METHODS: The 10%inhibitory concentration (IC10) of psoralen and its capacity to reverses multidrug resistance of the MCF-7/ADR cells were determined utilizing the MTT assay. The ability of psoralen to modulate the transport activity of P-gp in MCF-7/ADR cells was evaluated by detecting the accumulation and efflux of rhodamine123 ( Rh 123 ) and adriamycin (ADR) with flow cytometry (FCM). We evaluated the mRNA level of MDR1 among MCF-7/ADR treated with psoralen, MCF-7/ADR and MCF-7 cell lines by real time-PCR(RT-PCR).The expression of P-gp was examined by western blotting.Pgp-Glo assay systems were performed to assess the ATPase activity of P-gp.RESULTS: We found that the IC10 of psoralen for the MCF-7/ADR cells was 8?g/mL. At 8?g/mL, psoralen reversed MDR and the sensitivity of the MCF-7/ADR cells to ADR was 3.4 fold. Psoralen significantly increased the intracellular accumulation of ADR and Rh 123.However, the IC10 of psoralen did not affect the expression of P-gp and MDR1 (P >0.05).Additionally, we observed a significant decrease in ATPase activity caused by psoralen.CONCLUSION: Psoralen reverses P-gp-mediated MDR by inhibiting the efflux function of P-gp which are critical for the development of new MDR1 drugs and clinical protocols aimed at modulating P-gp-mediated multidrug resistance.