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Neferine increases STI571 chemosensitivity via inhibition of P-gp expression in STI571-resistant K562 cells.
MedLine Citation:
PMID:  21261505     Owner:  NLM     Status:  Publisher    
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 μM) and verapamil hydrochloride (VRP) (<10 μM) showed no direct cytotoxicity but significantly reduced the 50% cell growth inhibitory concentration (IC(50)) values of STI571 in K562/G01 cells. The reverse multiples for 8 μM Nef and 10 μM VRP were approximately two-fold. Both Nef (8 μM) and VRP (10 μM) 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.
Qun Qin; Xiao-Ping Chen; Zhou-Sheng Yang; Yu-Hang Xiao; Hui Min; Yuan-Jian Li
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-24
Journal Detail:
Title:  Leukemia & lymphoma     Volume:  -     ISSN:  1029-2403     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-1-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9007422     Medline TA:  Leuk Lymphoma     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.
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