title: [Effect of mPGES-1 inhibitor MK886 on apoptosis and drug resistance of HL-60/A cells].
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.
authors.affiliation: Department of Internal Hematology, Sun Yat-Sen University, Guangdong Province, China.
authors.forename: Yi-Qing
authors.initials: YQ
authors.lastname: Li
authors.forename: Song-Mei
authors.initials: SM
authors.lastname: Yin
authors.forename: Da-Nian
authors.initials: DN
authors.lastname: Nie
authors.forename: Shuang-Feng
authors.initials: SF
authors.lastname: Xie
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Ma
authors.forename: Xiu-Ju
authors.initials: XJ
authors.lastname: Wang
authors.forename: Yu-Dan
authors.initials: YD
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015973:Gene Expression Regulation, Leukemic; D018922:HL-60 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D002722:Chlorobenzenes
chemical_list: D007211:Indoles; C060893:MK-886; D002722:Chlorobenzenes