期刊
LEUKEMIA & LYMPHOMA
卷 52, 期 4, 页码 694-700出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/10428194.2010.550075
关键词
Leukemia; STI571; drug resistance; neferine; P-gp protein
资金
- National Natural Science Foundation of Hunan Province, China [08JJ5011]
We investigated the effects of neferine (Nef) on STI571 sensitivity and the possible mechanism in STI571-resistant K562/G01 cells. We observed cell proliferation by the modified MTT (methyl thiazolyl tetrazolium) assay. We determined the intracellular concentration of STI571 in K562/G01 cells by high-performance liquid chromatography (HPLC), the expression of P-glycoprotein (P-gp) by Western blotting, and the expression of MDR-1 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). We observed that drug resistance to STI571 for K562/G01 cells was 43.99-fold higher than that for K562 cells. We also observed that a low concentration of Nef (< 8 mu mu M) and verapamil hydrochloride (VRP) (< 10 mu mu M) showed no direct cytotoxicity but significantly reduced the 50%% cell growth inhibitory concentration (IC50) values of STI571 in K562/G01 cells. The reverse multiples for 8 mu mu M Nef and 10 mu mu M VRP were approximately two-fold. Both Nef (8 mu mu M) and VRP (10 mu mu M) decreased MDR-1 mRNA and P-gp protein expression and increased intracellular STI57I concentrations significantly in K562/G01 cells. Nef is a candidate chemical that can increase STI571 chemosensitivity in STI571-resistant K562 cells by inhibition of P-gp expression and increasing intracellular STI571 accumulation.
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