The Experimental Study Of Reversal Effect Of Multidrug Resistance By Medroxyprogesterone Acetate And Matrine On K562/AO2 Cell Line

Objective: This study was planned to observe the reversal effect of combination of medroxyprogesterone acetate and matrine on K562/AO2 cells, a adriamycin-resistant cell line of human leukemia. Methods : Cell toxicity and reversal times of medroxyprogesterone acetate and matrine on tumor cells were determined by MTT assay. Intracellular drug concentration and cell apoptosis percentage were determined by spectrophotofluorometry and flow cytometry respectively. Changes of P-gp were determined by flow cytometry. Results: (1)Non-cytotoxic dosage and low-cytotoxic dosage of medroxyprogesterone acetate and matrine were determined by MTT assay. There is no addition toxic when Non- cytotoxic of medroxyprogesterone acetate combined with matrine.(2)Used along with adtiamycin ,cell apoptosis percentage of K562/AO2 with medroxyprogesterone acetate or matrine was higher than that of K562/AO2 (P<0.05,P<0.01 respectivly),but still lower than that of K562/AO2 with medroxyprogesterone acetate and matrine (P<0.01, P<0.05 respectively).(3)Compared with K562 cells, P-gp overexpress in K562/AO2; Compared with K562/AO2, intracellular P-gp content were lower in K562/AO2 with medroxyprogesterone acetate and K562/AO2 with matrine(P<0.01), but the P-gp expression in K562/AO2 with medroxyprogesterone acetate and matrine were lower than that of K562/AO2 With medroxyprogesterone acetate or matrine respectively.(4)Compared with adriamycin , medroxyprogesterone acetate and matrine can significantly enhance intracellular adriamycin concentration (P<0.01 respectively);The effect of combination of two agents were superior to that of single uses. Conclusion : Non-cytotoxic dosage of medroxyprogesterone acetate and matrine could partly reverse the MDR of K562/AO2;The effect of combination of two agents were superior to that of single uses due to their coordinate effect; and consequently ,the adriamycin related cytotoxicity that showed in cellular apoptosis ratio in K562/AO2 was harply ascended. Overexpression of P-gp in K562/AO2 were related to mechanism of multidrug resistance.