Effects of imatinib and 5-bromotetrandrine on the reversal of multidrug resistance of the K562/A02 cell line.
Chin J Cancer
; 29(6): 591-5, 2010 Jun.
Article
em En
| MEDLINE
| ID: mdl-20507731
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Piperazinas
/
Pirimidinas
/
Membro 1 da Subfamília B de Cassetes de Ligação de ATP
/
Resistência a Múltiplos Medicamentos
/
Resistencia a Medicamentos Antineoplásicos
/
Benzilisoquinolinas
Limite:
Humans
Idioma:
En
Revista:
Chin J Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2010
Tipo de documento:
Article