Reversal Effect Of Acridine Compound T19 On Multidrug Resistance In K562/ADR And MCF-7/ADR Cells

Objective: To investigate the role of acridine compounds T19 in reversing the multidrug resistance of K562/ ADR and MCF-7/ ADR cells and their related mechanisms.Methods: MTT method was used to screen the ADR to inhibit the survival of K562,K562/ ADR,MCF-7 and MCF-7/ ADR cells.To investigate the effect of acridine compound T19 on the proliferation of K562/ ADR and MCF-7/ ADR cells by the effect of acridine compound T19 on the proliferation of four kinds of cells.The effect of acridine compound T19 on P-gp function and expression of K562/ ADR and MCF-7/ ADR cells was detected by flow cytometry and Wenstern Blot.The expression of P-gp in K562/ ADR,MCF-7/ ADR cells was detected by flow cytometry and Wenstern Blot assay.The expression of P-gp in K562/ ADR and MCF-7/ ADR cells was analyzed by flow cytometry and Wenstern Blot.influences.The effect of compound T19 and PI3K/ Akt inhibitor LY294002 and HO-1 inhibitor Znpp on the expression of P-Akt,HO-1 and P-gp protein in K562/ ADR and MCF-7/ ADR cells were studied by using Wenstern Blot.Compound T19 reverses the mechanism of MDR.Results: 1.The acridine compound T19 increased the sensitivity of K562/ ADR,MCF-7/ ADR cells to ADR.And then reversed the multidrug resistance of K562/ ADR,MCF-7/ ADR cell lines.2.The acridine compound T19 can significantly down-regulate K562/ ADR,MCF-7/ ADR cell line P-gp function and expression and in a concentration-dependent.3.The acridine compound T19 to down-regulate K562/ ADR,MCF-7/ ADR cells P-gp function and expression by inhibiting PI3K/ Akt/ HO-1 signal pathway.Conclusion: The function and expression of P-gp were down-regulated by PI3K/ Akt/ HO-1 signal pathway,and the MDR effect of K562/ ADR and MCF-7/ ADR cells was reversed.