[Mechanisms of Astragalus Polysaccharids Synergized with Doxorubicin against Drug Resistance in HL-60/A Cells].

OBJECTIVE: To explore the synergistic anti-tumor mechanism of astragalus polysaccharids(APS) combined with doxorubicin in HL-60/A cells.

METHODS: The phenotype of HL-60/A was identified by using RT-PCR, Wester blot and CCK-8, the antitumor effect of astragalus polysaccharids combined with doxorubicin on HL-60/A cells was detected by CCK-8, the apoptosis of HL-60/A after treating with different drugs was detected by Annexin-V, the caspase casade activation was detected by Wester blot, the effect of astragalus polysaccharids on expression and function of multidrug resistance protein (MRP) was detected by using real-time quantitative PCR and Western blot.

RESULTS: HL-60/A cells displayed obvious characteristics of resistance to doxorubicin, whose resistance were about 27 times that of its sensitive cell line HL-60. In addition, it was further found that astragalus polysaccharids could obviously increase the cell growth inhibition, induce cell apoptosis and caspase cascade activation, decrease the expression of MRP and increase the drug concentration in HL-60/A when combined with doxorubicin.

CONCLUSION: Astragalus polysaccharids combined with doxorubicin can effectively overcome the drug resistance of HL-60/A. The mechanism may be associated with decreasing the expression of MRP, inhibiting drug efflux and increasing the intracellular drug concentration, then inducing HL-60/A cell apoptosis.