AIM To observe the reversal effects of Ganoderma lucidum polysaccharide (Gl-PS) on multidrug resistance (MDR)to K562/A in vitro and in vitro.To investigate the mechanism of MDR-reversal effect on Gl-PS.METHODS In vitro, K562/A cells were cultured for 2 weeks in ADM-frec medium prior to the experiment.The resistance index of the K562/A cells toward ADM was detected by CCK-8 test.The reversal effect of Gl-PS (50, 100 and 200 mg·L-1) on the multidtug K562/A cell toward ADM was detected by CCK-8 test.The protein expression of GST-π was determined by Western blot, and the early apoptosis effect of Gl-PS onK562/A was detected by Annexin V staining.In vivo, K562/A cells in the logarithmic growth phase were subcutaneously injected in the right flank of nude mice, and the parent K562 cells were subcutaneously injected in the left flank of the nude mice.Each injection contained 1 × 107 cells.The nude mice were divided into seven groups: saline control group, verapamil combined with ADM group,ADM group, Gl-PS (100 mg·kg-1) group, Gl-PS (50, 100 and 200 mg·kg-1) combined with ADM group, respectively.Tumor GST-π mRNA expression was determined by reverse-transcriptase polymerase chain reaction (RT-PCR).The expression of GST-π and caspase 3 was assayed by Western blot.RESULTS IC50 of K562/A and K562 to ADM were 38.33 and0.78 mg·L-1 , respectively.Gl-PS (50, 100 and 200 mg·L-1) could decrease the IC50 of K562/A to ADM, IC50 of K562/A to ADM were 28.05, 24.21 and 23.61 mg· L-1, respectively.Gl-PS (100 and 200 mg· L-1) could effectively reverse MDR-resistance (P < 0.05).Gl-PS (50, 100and 200 mg·L-1) could not effectively decrease the IC50 of K562 to ADM.Gl-PS (100 and 200 mg·L-1) could decrease the protein expression of GST-π in vitro (P < 0.05), while Gl-PS could not significantly change the protein level of GST-π.Gl-PS (100 and 200 mg· L-1) could significantly induce the early apoptosis of K562/A in vitro (P < 0.05).After administration of Gl-PS (50, 100and 200 mg·kg-1) combined with ADM for 14 d, the groups of middle and high dose could significantly inhibit the growth of K562/A tumor (P < 0.05).GST-π mRNA expression of K562/A tumor was higher than that of K562.The Gl-PS group of high dose could significantly decrease GST-π mRNA expression of K562/A tumor (P < 0.01).After administration of Gl-PS (50, 100 and 200 mg·kg-1) combined with ADM for 14 d, the groups of middle and high dose could significantly inhibit GST-π protein expression of K562/A tumor (P < 0.05), increase cleaved caspase 3 protein expression of K562/A tumor (P < 0.05).CONCLUSION Gl-PS could reversal multidrug resistance of K562/A in vitro, the effect of Gl-PS was linked to decrease the IC5o of K562/A to ADM, downregulation of GST-π protein expression and induce the early apoptosis of K562/A.Gl-PS enhances the sensitivity of K562/A tumor tocytotoxic killing by the therapeutic drug ADM, and inhibits the growth of tumor.The tumor growth inhibition induced by Gl-PS is associated with down regulation of GST-π expression.The activation of caspase 3 also contributes to the effect of Gl-PS.