Effects of RNA Targeting mPGES-1 on Proliferation and Apoptosis of K562/A Cells
- VernacularTitle:RNA 干扰 mPGES-1 基因对 K562/A 细胞增殖及凋亡的影响
- Author:
Meng QIU
1
;
Da-nian NIE
1
;
Shuang-feng XIE
1
;
Jie XIAO
1
;
Yu-dan WU
1
;
Xiu-ju WANG
1
;
Wen-juan YANG
1
;
Yi-qing LI
1
Author Information
1. Department of Internal Hematology，Sun Yat-Sen Memorial Hospital，Sun Yat-Sen University//Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation，Guangzhou 510120，China
- Publication Type:Journal Article
- Keywords:
mPGES-1, PGE2, leukemia, drug-resistance, β-catenin
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2020;41(2):233-242
- CountryChina
- Language:Chinese
-
Abstract:
【Objective】 To explore the effects and the possible mechanism of RNA targeting membrane-bound prostaglandin E2 synthase l（mPGES- 1）on proliferation，apoptosis and drug resistance of leukemia cell line K562/A.【Methods】RNA interference was used to inhibit the expression of mPGES-1 of K562/A cells. Four groups were set up as follows：untreated group（K562/A），negative control group after interference（K562/A-NC），group after interference（K562/ A-KD），and group after interference with exogenous PGE2（K562/A-KD+PGE2）.Cell viability was assessed by CCK-8 assay. Cell apoptosis was analyzed by flow cytometry. Concentration of PGE2 was detected by ELISA. Proteins expression was detected by western blot.【Results】The expression of mPGES- 1 in K562/A cells was significantly down- regulated and the synthesis of PGE2 decreased（P < 0.000 1）after RNA interference. After RNA interference，the proliferation of K562/A cells was inhibited and apoptosis increased，and the sensitivity to chemotherapy drugs was enhanced（P < 0.05）. Meanwhile，the expression of β-catenin and MDR1 was decreased（P < 0.01）. Exogenous PGE2 could reverse the effect of RNA interference on proliferation ，apoptosis and drug sensitivity in K562/A cells（P < 0.05），and up-regulate the expression of β-catenin and MDR1（P < 0.01）. XAV939，an inhibitor of β-catenin，could down-regulate the expression of β- catenin and MDR1 in an dose- dependent pattern in K562/A cells（P < 0.05）.【Conclusions】RNA interference of mPGES- 1 could inhibit proliferation，induce apoptosis and reverse drug resistance in K562/A cells. The mechanism was related to reducing the synthesis of PGE2 and thus down- regulating the expression of β- catenin and MDR1. Wnt/β- catenin signal pathway may participate in the regulation of MDR1 by mPGES-1/PGE2.
