Jiantao Ye1, Yilei Zheng, Deyu Liu. 1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510089, China.
Abstract
OBJECTIVE: To investigate the inhibitory effect of ampelopsin (AMP) combined with adriamycin (ADR) on growth of human leukemia multidrug resistant cell line K562/ADR. METHOD: MTT assay was used to detect the effect of AMP on the cytotoxicity of ADR. Jin's formula was used to analyze the effect of combined drug therapy. The expression of P-glycoprotein (P-gp) on cell membrane of K562/ADR was detected using PE-labeled antibody. Flow cytometry was used to determine the influence of AMP on the intracellular accumulation of ADR. RESULT: AMP at the concentration of 1.25 to 5 mg x L(-1) could significantly reverse the multidrug resistance (MDR) to ADR in K562/ADR cells. Co-administration of 1.25 mg x L(-1) AMP and low concentrations of ADR showed an antagonistic effect, while there was an additional to synergistic effect when the concentration of AMP was above 2.5 mg x L(-1). AMP could decrease the expression of P-gp in a concentration-dependent manner and increase the intracellular accumulation of ADR in K562/ADR cells. CONCLUSION: AMP could increased the cytotoxicity and the intracellular accumulation of chemotherapeutic drugs in MDR associated tumor cells through inhibiting the efflux of drugs by P-gp. AMP may be a promising MDR modulator.
OBJECTIVE: To investigate the inhibitory effect of ampelopsin (AMP) combined with adriamycin (ADR) on growth of humanleukemia multidrug resistant cell line K562/ADR. METHOD:MTT assay was used to detect the effect of AMP on the cytotoxicity of ADR. Jin's formula was used to analyze the effect of combined drug therapy. The expression of P-glycoprotein (P-gp) on cell membrane of K562/ADR was detected using PE-labeled antibody. Flow cytometry was used to determine the influence of AMP on the intracellular accumulation of ADR. RESULT: AMP at the concentration of 1.25 to 5 mg x L(-1) could significantly reverse the multidrug resistance (MDR) to ADR in K562/ADR cells. Co-administration of 1.25 mg x L(-1) AMP and low concentrations of ADR showed an antagonistic effect, while there was an additional to synergistic effect when the concentration of AMP was above 2.5 mg x L(-1). AMP could decrease the expression of P-gp in a concentration-dependent manner and increase the intracellular accumulation of ADR in K562/ADR cells. CONCLUSION:AMP could increased the cytotoxicity and the intracellular accumulation of chemotherapeutic drugs in MDR associated tumor cells through inhibiting the efflux of drugs by P-gp. AMP may be a promising MDR modulator.