The Effect Of Borneol And Isoborneol On The Drug Resistance Reversal Of MCF-7/ADR And The Effect Of P-glycoprotein Expression

Overcoming multidrug resistance caused by P-glycoprotein is an important way to improve the clinical tumor effect of chemotherapy.In this study,we investigated the reversal effect of multidrug resistant of borneol and isoborneol in breast cancer cell MCF-7/ADR with adriamycin as model drug,as well as the function and expression of efflux protein P-gp.And we further discussed the the possible mechanism of borneol and isoborneol of multidrug resistance reversal.The reversal effects were observed by determining the inhibition rates of cell viability with MTT assays.The intracellular accumulation of ADR was detected via confocal laser scanning microscope(CLSM).P-gp activity was evaluated by measuring the intracellular accumulation of Rhodamine 123(Rh123)by flow cytometer(FCM).The expressions of P-gp at the protein level and MDR1 mRNA were detected by flow cytometer and RT-qPCR,respectively.The results showed that MCF-7 and MCF-7/ADR cells survialed more than 98%after co-culturing with borneol and isoborneol(10 ?M?400 ?M),and it showed low cytotoxic effect.So,we chosed concertrations of 50,150 and 300?M for next experiments.After incubation for 48 hours with 300 ?M,the maximum experimental concentration of borneol and isoborneol,IC50 of ADR in MCF-7/ADR cells was decreased from 156.17 ?M to 4.10?M(borneol)and 8.49 ?M(isoborneol).ADR intracellular accumulation in MCF-7/ADR cells increased from 21.06%to 86.63%(borneol)and 68.86%(isoborneol)Rh123 accumulations in MCF-7/ADR cells increased in a concentration-dependent manner to 65.12%and 51.49%.A significant down-regulation was observed from borneol group or isoborneol group in P-gp expression(most reduce 57.74%and 49.35%,respectively),and in MDR1 mRNA expression(43.67%and 54.78%,respectively).Significantly statistical difference could be observed from the data which proved the borneol was more effective than isoborneol.These results indicated that borneol and isoborneol could cut the expression of P-gp which affects the function of P-gp by inhibiting the expression of MDR1 mRNA levels.Both borneol and isoborneol could be potential MDR-reversing agents in the human breast cancer chemotherapy.