Reversal effect and its mechanism of ampelopsin on multidrug resistance in K562/ADR cells.
- Author:
Jiantao YE
1
;
Yilei ZHENG
;
Deyu LIU
Author Information
- Publication Type:Journal Article
- MeSH: ATP-Binding Cassette, Sub-Family B, Member 1; metabolism; Animals; Antineoplastic Agents; metabolism; pharmacology; Cell Line, Tumor; Cell Proliferation; drug effects; Doxorubicin; metabolism; pharmacology; Drug Resistance, Multiple; drug effects; Drug Resistance, Neoplasm; drug effects; Flavonoids; pharmacology; Gene Expression Regulation, Neoplastic; drug effects; Humans; Intracellular Space; drug effects; metabolism
- From: China Journal of Chinese Materia Medica 2009;34(6):761-765
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the inhibitory effect of ampelopsin (AMP) combined with adriamycin (ADR) on growth of human leukemia multidrug resistant cell line K562/ADR.
METHODMTT 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.
RESULTAMP 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.
CONCLUSIONAMP 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.