Study on reversal effect of nilotinib in combination with 5-BrTet on multidrug resistance of K562/A02 cell line / 中华血液学杂志
Chinese Journal of Hematology
;
(12): 385-388, 2010.
Article
in Chinese
| WPRIM
| ID: wpr-353587
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the reversible effect of nilotinib, BrTet (5-bromotetrandrine) and their combination on multidrug resistance cell line K562/A02 and its mechanism.</p><p><b>METHODS</b>Cell proliferation inhibition was assessed by MTT method and cell apoptosis by flow cytometry (FCM). The expression of mdr1 mRNA was determined by RT-PCR, and the expression of P-gp was assessed by Western blot.</p><p><b>RESULTS</b>After 48 h 5 nmol/L nilotinib or 0.5 µmol/L BrTet treatment, IC(50) of daunorubicin (DNR) to K562/A02 was 4.52 mg/L or 5.41 mg/L respectively; While on combinative treatment, its IC(50) decreased to 2.98 mg/L. Nilotinib or BrTet alone was not able to increase the DNR induced apoptosis rate of K562/A02 cell (P > 0.05), while on combination treatment the apoptosis rate increased remarkably. After 48 h 5 nmol/L nilotinib or 0.5 µmol/L BrTet treatment alone, gray-scale value of mdr1 mRNA was 0.48 ± 0.04 or 0.64 ± 0.01, respectively; while on combinative treatment the value decreased to 0.35 ± 0.04. The P-gp expression level in K562/A02 cells was 0.61 ± 0.05, or 0.52 ± 0.02 when treated with 5 nmol/L nilotinib or 0.5 µmol/L BrTet alone for 48 h, but on combination treatment, the level decreased to 0.44 ± 0.03.</p><p><b>CONCLUSION</b>Nilotinib or BrTet alone can partially reverse drug resistance of K562/A02 cells. The mechanism may be associated with the decrease of mdr1 mRNA and P-gp expression and increase of the apoptosis rate. And there is a synergistic action with these two agants in combination.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Daunorubicin
/
ATP Binding Cassette Transporter, Subfamily B, Member 1
/
Drug Resistance, Multiple
/
Drug Resistance, Neoplasm
/
K562 Cells
/
Metabolism
Limits:
Humans
Language:
Chinese
Journal:
Chinese Journal of Hematology
Year:
2010
Type:
Article
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