Reversal Effect of Pioglitazone on Multidrug Resistance in K562/ADR Cells and Its Mechanism.
10.19746/j.cnki.issn.1009-2137.2019.03.023
- Author:
Cheng ZHANG
1
;
Ding-Ming WAN
2
;
Wei-Jie CAO
2
;
Yang ZHANG
1
;
Hui-Bing DANG
1
;
Yu-Jing WEI
3
Author Information
1. Department of Hematology, The First Affiliated Hospital of Nanyang Medical College. Nanyang 473000, Henan Province, China.
2. Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
3. Department of Hematology, The First Affiliated Hospital of Nanyang Medical College. Nanyang 473000, Henan Province, ChinaE-mail: weiyjnyyz@163.com.
- Publication Type:Journal Article
- MeSH:
Doxorubicin;
Drug Resistance, Multiple;
Drug Resistance, Neoplasm;
Humans;
K562 Cells;
Pioglitazone
- From:
Journal of Experimental Hematology
2019;27(3):785-789
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the reversal effect of pioglitazone (PIO) on multidrug resistance in K562/ADR cells and its mechanism.
METHODS:The proliferation inhibition rate, half inhibition concentration (IC) and drug-resistance reversal multipe were detected and the curve of proliferation inhibition rate was drawn by MTT assay, the transcription of PPARγ, CYP2C8 and CYP2J2 genes was detected by RT-PCR; the expression of PPARγ, CYP2C8 and CYP2J2 proteins was detected by Western blot.
RESULTS:The IC of PIO on K562 and K562/ADR cells for 60 h was 326.7 μmol/L and 349.1 μmol/L respectively. The reversal multiple of 30 μmol/L PIO on ADR-resistance of K562/ADR cells was 6.4. After treatment of K562/ADR cells with PIO, the transcription of CYP2C8 and CYP2J2 and the protein expression of CYP2C8 and CYP2J2 significantly decreased, the transcription of PPARγ gene and the expression of PPARγ protein were not changed.
CONCLUSIONS:Pioglitazone can reverse the adriamycin-resistance in K562/ADR cells that is closely related to the decrease of protein expression of CYP2C8 and CYP2J2. Pioglitazone is an effective multidrug resistance reversal agent for tumors.