Study of mifepristone on reversing multidrug resistance of leukemic cell line K562/A02 / 中华血液学杂志
Chinese Journal of Hematology
;
(12): 555-559, 2007.
Article
in Chinese
| WPRIM
| ID: wpr-262984
ABSTRACT
<p><b>OBJECTIVE</b>To study whether progestogen antagonist mifepristone could reverse multidrug resistance of K562/A02 cells and its mechanisms.</p><p><b>METHODS</b>MTT was used to study the proliferation of K562/A02 cells and sensitivity of K562/A02 cells to ADM after 72 hours treatment with mifepristone. Flow cytometry was used to assay the expression of P-glycoprotein and the mean fluorescent intensity of intracellular daunorubicin. The expressions of apoptosis related proteins (bcl-2, Bax and caspase-3) were assayed by immunohistochemistry and the glucosylceramide synthase mRNA expression by RT-PCR before and after mifepristone treatment.</p><p><b>RESULTS</b>MTT assay revealed that 2.5, 5.0 and 10 micromol/L mifepristone did not affect the proliferation of K562/A02 cells, but enhanced the sensitivity of K562/A02 cells to ADM, by 1. 68-, 4.17- and 10.71- fold increase, respectively. Expression of P-gp in K562/A02 cells was (49.03 +/- 5.32)%, and was decreased to (28.60 +/- 2.13)% (P < 0.01) after 10 micromol/L mifepristone treatment for 72 hours. and intracellular DNR accumulation in K562/A02 was (61.07 +/- 8.61)%, and was increased to (92.72 +/- 3.48)% (P < 0.01). After 10 micromol/L mifepristone treatment, the expression of bcl-2 protein was decreased from (56 +/- 9)% to (37 +/- 6)% (P < 0.05), Bax and caspase-3 proteins was increased from (40 +/- 5)% to (87 +/- 10)% (P < 0.01), and from (36 +/- 7)% to (89 +/- 6)% (P < 0.01) respectively. RT-PCR analysis revealed that expression of glucosylceramide synthase mRNA was higher in K562/A02 than in K562 cells, whereas 10 micromol/L mifepristone significantly down-regulated its expression in K562/A02 cells.</p><p><b>CONCLUSION</b>Mifepristone at 10 micromol/L could dose-dependently reverse the multidrug resistance of K562/A02 cells. The possible mechanisms are related with decreasing the expression of P-gp, regulating the expression of apoptosis related proteins and decreasing the expression of glucosylceramide synthase.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
RNA, Messenger
/
Pharmacokinetics
/
Daunorubicin
/
Doxorubicin
/
Mifepristone
/
ATP Binding Cassette Transporter, Subfamily B, Member 1
/
Drug Resistance, Multiple
/
Drug Resistance, Neoplasm
/
K562 Cells
Limits:
Humans
Language:
Chinese
Journal:
Chinese Journal of Hematology
Year:
2007
Type:
Article
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