Effect of mPGES-1 inhibitor MK886 on apoptosis and drug resistance of HL-60/A cells.
- Author:
Yi-Qing LI
1
;
Song-Mei YIN
;
Da-Nian NIE
;
Shuang-Feng XIE
;
Li-Ping MA
;
Xiu-Ju WANG
;
Yu-Dan WU
Author Information
1. Department of Internal Hematology, Sun Yat-Sen University, Guangdong Province, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
drug effects;
Cell Proliferation;
drug effects;
Drug Resistance, Neoplasm;
drug effects;
Gene Expression Regulation, Leukemic;
HL-60 Cells;
Humans;
Indoles;
pharmacology
- From:
Journal of Experimental Hematology
2012;20(4):829-834
- CountryChina
- Language:Chinese
-
Abstract:
This study was aimed to investigate the effect of MK886, a mPGES-1 inhibitor, on apoptosis and drug resistance of leukemia HL-60/A cell line. Expression of mPGES-1 was assayed by QT-PCR and Western blot. The effect of MK886 on HL-60/A cell proliferation was assayed by CCK-8 method, and flow cytometry was used to detect cell apoptosis. The expression of Akt and P-Akt was detected by Western blot. PGE2 was measured by ELISA. Effect of MK886 (10 µmol/L) on the chemotherapeutic sensitivity of HL-60/A cells and expression of mdr-1 mRNA and P170 protein were investigated too. The results indicated the expression of mPGES-1 was higher in HL-60/A cells. MK886 inhibited HL-60/A cell proliferation and induced apoptosis in a time- and concentration-dependent manner. Expression of mPGES-1 and P-Akt and synthesis of PGE2 decreased significantly. MK886 reduced expression of mdr-1 and P170 protein and enhanced the sensitivity of HL-60/A cells to chemotherapeutic drugs. It is concluded that MK886 can inhibit HL-60/A cell proliferation, induce apoptosis and enhance sensitivity to chemotherapeutic drugs, the mechanism of which possibly associates to down-regulation of mPGES-1/PGE2 synthesis, reduction P-Akt expression and decreasing mdr-1 and P170 protein expression.
