Document Detail


Effects of imatinib and 5-bromotetrandrine on the reversal of multidrug resistance of the K562/A02 cell line.
MedLine Citation:
PMID:  20507731     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND OBJECTIVE: Research has shown that 5-bromotetrandrine (BrTet) can effectively reverse multidrug resistance (MDR). Imatinib plays an important role in cell proliferation. This study explored the efficacy of the combination of imatinib and BrTet on reversing MDR of tumor cells and its mechanism.
METHODS: Cytoxicity was assessed by MTT assay. Apoptosis of K562/A02 cells was analyzed by flow cytometry. The expressions of mdr1 mRNA and P-glycoprotein (P-gp) were detected using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis.
RESULTS: After 48 h of treatment with 0.0625 micromol/L imatinib, 0.5 micromol/L BrTet, or both, the 50% inhibition concentration (IC50) of daunorubicin (DNR) for the K562/A02 cells were 5.69 mg/L, 5.41 mg/L, and 2.19 mg/L, respectively. The gray-scale values of mdr1 mRNA expression in the K562/A02 cells were 0.65+/-0.02, 0.64+/-0.01, and 0.25+/-0.03, respectively. The expression levels of P-gp were 0.74+/-0.02, 0.52+/-0.02, and 0.29+/-0.02, respectively. All decreased significantly in the K562/A02 cells treated with both imatinib and BrTet compared to cells treated with imatinib and BrTet alone (P<0.05). The apoptosis rates of the K562/A02 cells increased without a significant difference after treatment with DNR, imatinib, or BrTet (P>0.05), while increased significantly after treatment with DNR combined with imatinib, BrTet, or both (P<0.05).
CONCLUSIONS: The MDR of K562/A02 cells may be partially reversed by imatinib or BrTet, and the mechanism may be related to the downregulation of mdr1 mRNA and P-gp expression and the upregulation of the rate of apoptosis in K562/A02 cells. Imatinib combined with BrTet showed a synergistic effect on K562/A02 cells.
Authors:
Bao-An Chen; Xue-Yun Shan; Jian Chen; Guo-Hua Xia; Wen-Lin Xu; Michael Schmit
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chinese journal of cancer     Volume:  29     ISSN:  1000-467X     ISO Abbreviation:  Chin J Cancer     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-28     Completed Date:  2012-01-05     Revised Date:  2013-02-12    
Medline Journal Info:
Nlm Unique ID:  101498232     Medline TA:  Chin J Cancer     Country:  China    
Other Details:
Languages:  eng     Pagination:  591-5     Citation Subset:  IM    
Affiliation:
Department of Hematology, Zhongda Hospital, Medical College, Southeast University, Nanjing, Jiangsu 210009, PR China. cba8888@hotmail.com
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MeSH Terms
Descriptor/Qualifier:
Antibiotics, Antineoplastic / pharmacokinetics,  pharmacology
Antineoplastic Agents / pharmacology
Apoptosis / drug effects
Benzylisoquinolines / pharmacology*
Cell Proliferation / drug effects
Daunorubicin / pharmacokinetics,  pharmacology
Down-Regulation
Drug Resistance, Multiple / drug effects*
Drug Resistance, Neoplasm / drug effects*
Drug Synergism
Gene Expression Regulation, Leukemic
Humans
K562 Cells / drug effects
P-Glycoprotein / genetics,  metabolism*
Piperazines / pharmacology*
Pyrimidines / pharmacology*
RNA, Messenger / metabolism
Chemical
Reg. No./Substance:
0/ABCB1 protein, human; 0/Antibiotics, Antineoplastic; 0/Antineoplastic Agents; 0/Benzylisoquinolines; 0/P-Glycoprotein; 0/Piperazines; 0/Pyrimidines; 0/RNA, Messenger; 0/bromotetrandrine; 20830-81-3/Daunorubicin; BKJ8M8G5HI/imatinib

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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