Effect Of The Total Saponins From Solanum Nigrum L. On Reversing Multidrug Resistance On K562/ADR Cells And Its Mechanisms

Aim: Multidrug resistance(MDR)interferes severely with the efficiency of leukemia oncology progress.As a traditional Chinese folk medicine,Solanum nigrum L.has been widely used in tumor treatment and achieve great progress in leukemia chemotherapy.The steroidal saponins(SN)are its main bioactive constituents,yet its molecular mechanism remains to be revealed.This study aims to determine the reversal activity of SN on multidrug resistant K562/ADR cells and elucidate its underlying mechanisms.Methods: MTT assay was used to evaluate the reversal effect of SN on K562/ADR cell line.Flow cytometry was performed to measure the accumulation of ADR and Rhod123 in K562/ADR cells and it was also used to analyze cell apoptosis and reactive oxygen species expression level after SN treatment.Western blot was used to detect the expression of proteins related to multidrug resistance,apoptosis and autophagy.Furthermore,K562/ADR xenograft model was established to assess the multidrug resistance reversal effect of SN in vivo.Result: The combination of SN and ADR inhibited tumor progression on K562/ADR xenograft model and reduced cell viability rate of K562/ADR cell in vitro.Further study showed that SN inhibited the function of P-gp and downregulated the proteins related to multidrug resistance.The combination of SN and ADR induced cell apoptosis in K562/ADR cells through caspase pathways and autophagy through PI3K/Akt/m TOR and MAPK signaling pathway.Conclusion: It was indicated that SN reverse multidrug resistance in K562/ADR cells,offering a new strategy to the application of SN on leukemia treatment.