The study on reversing mechanism of multidrug resistance of K562/A02 cell line by curcumin and erythromycin.
- Author:
Hong-yu CHANG
1
;
Kai-li PAN
;
Fu-cheng MA
;
Xi-ying JIAO
;
Hua-feng ZHU
;
Jian-hong LIU
;
Ying HUANG
;
Yu-hong CAO
Author Information
- Publication Type:Journal Article
- MeSH: ATP-Binding Cassette, Sub-Family B, Member 1; genetics; metabolism; Antineoplastic Agents; pharmacology; Cell Proliferation; drug effects; Cell Survival; drug effects; Curcumin; pharmacology; Drug Resistance, Multiple; drug effects; Drug Resistance, Neoplasm; drug effects; Drug Synergism; Epirubicin; pharmacology; Erythromycin; pharmacology; Gene Expression Regulation, Neoplastic; drug effects; Humans; Immunohistochemistry; K562 Cells; Leukemia, Erythroblastic, Acute; genetics; metabolism; pathology; RNA, Messenger; genetics; metabolism; Reverse Transcriptase Polymerase Chain Reaction; Time Factors
- From: Chinese Journal of Hematology 2006;27(4):254-258
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effects of curcumin (Cur) and erythromycin (EM) on multidrug resistance (MDR) reversal of K562/A02 cell line and their mechanism.
METHODSMTT assay was employed to determine the sensitivity of Cur, EM-treated K562/A02 cells to adriamycin (ADM). Flow cytometry was used to measure intracellular mean fluorescence intensity (MFI) of daunorubicin (DNR). P-gp expression was determined by immunohistochemistry. RT-PCR technique was used to examine the mdr1 mRNA level.
RESULTSIC(50) of ADM in K562/A02 cells was decreased when treated with Cur or EM, and the reversal times (RvT) was 4.9, 3.7 respectively. The RvT reached to 11.3 when treated with Cur (2.5 microg/ml) combined with EM (120 microg/ml). The DNR MFI in K562/A02 cells was significantly lower than that in K562 cells (P < 0.01), and was increased significantly when treated with Cur (2.5 microg/ml) or EM (120 microg/ml) (P < 0.05). There was no significant difference between DNR MFI of K562/A02 cells treated with Cur (2.5 microg/ml) or EM (120 microg/ml). Immunohistochemistry showed that P-gp expression was significantly higher in K562/A02 cells than in K562 cells (P < 0.01), and was reduced in K562/A02 cells treated with each (P < 0.01), though being still higher than that in K562 cells (P < 0.01). P-gp expression of K562/A02 cells treated with each drug for 5 days were lower than that for 3 days (P < 0.01), and lowered further when treated with Cur and EM together (P < 0.01). Mdr1 mRNA level in K562/A02 cells was higher than in K562 cells (P < 0.01), and was decreased when treated with each of the drugs (P < 0.01). The mdr1 mRNA level of K562/A02 cells treated with Cur (2.5 microg/ml) plus EM (120 microg/ml) was decreased most significantly than that treated with other group of drugs. After 5 day treatment the mdr1 mRNA level of K562/A02 cells with Cur (2.5 microg/ml) was lower than that with EM 120 microg/ml (P < 0.01).
CONCLUSIONSEither Cur or EM can partly reverse the multidrug resistance of K562/A02 cells and decrease the expression and function of P-gp in a time-dependent way. MDR reversing effect of Cur combined with EM is stronger than that of Cur or EM alone.
