Mechanism of Anti Apoptosis and Immune Evasion in Drug-Resistant Leukemia Cells Mediated by STAT3.
10.19746/j.cnki.issn.1009-2137.2020.06.002
- Author:
Zhu-Xia JIA
1
;
Xu-Zhang LU
1
;
Jin-Yuan HE
1
;
Xiao-Hui CAI
1
;
Wei QIN
1
;
Wen-Min HAN
1
;
Min ZHOU
2
;
Wei XU
3
Author Information
1. Department of Hematology, The Affiliated Hospital of Nanjing Medical University, Changzhou No.2 People's Hospital, Changzhou 213000, China.
2. People's Hospital, Changzhou 213000, China; 2Changzhou No.3 People's Hospital, Changzhou 213000, Jiangsu Province, China.
3. Department of Hematology, The First Affiliated Hospital of Nanjing Medical University(Jiangsu Province Hospital), Nanjing 210029, China,E-mail：xuwei10000@hotmail.com.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
Humans;
Immune Evasion;
K562 Cells;
Killer Cells, Natural;
Leukemia;
Pharmaceutical Preparations;
STAT3 Transcription Factor
- From:
Journal of Experimental Hematology
2020;28(6):1796-1803
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the mechanisms of anti-apoptosis and immune evasion in drug-resistant leukemia cells mediated by STAT3, further to explore the possible mechanism of leukemia relapse caused by minimal residual.
METHODS:Drug-resistance leukemia cell line was established by transfecting pcDNA3.1-STAT3 into K562 cells (K562/STAT3). The expression of STAT3, BAX and NKG2D ligands (MICA and ULBP1) in K562/-cells, K562/STAT3 were detected by Western blot and/or RQ-PCR. Cells apoptosis and the killing effect of NK cells on leukemia cells were detected by flow cytometry.
RESULTS:The expression of the total STAT3, STAT3 phosphorylation in K562/STAT3 was significantly increased, and P-gp mRNA expression was increased also significantly (P<0.005). In K562/STAT3 cells, the expression of pro-apoptotic BAX (P=0.005) was significantly lower, and the number of apoptotic cells (P=0.002) induced by adriamycin was significantly decreased as compared with those in K562/- cells. After K562/STAT3 cells were treated by STAT3 inhibitor (SH-4-54), the expression of BAX mRNA (P=0.017) was significantly higher and the number of apoptotic cells (P=0.005) was significantly increased. The MICA and ULBP1 mRNA expression in K562/STAT3 cells was significantly lower than that in K562/- cells, and also for MICA and ULBP1 protein (MICA and ULPB1 mRNA: P<0.0001, MICA protein: P=0.001, ULPB1 protein: P=0.022). After K562/STAT3 cells were treated with STAT3 inhibitor (SH-4-54), the expression of MICA mRNA and protein was increased (mRNA: P=0.001, protein: P=0.002), but ULBP1 mRNA and protein showed no significantly change (mRNA: P=0.137, protein: P=0.1905). The cytotoxicity of NK cells to K562/STAT3 cells was susceptible as compared with K562/- (P=0.002), but the cytotoxicity of K562/STAT3 cells to NK cell could be recovered by STAT3 inhibitor (P=0.006).
CONCLUSION:STAT3 phosphorylation can inhibits cell apoptosis and promotes cell immune escape. STAT3 inhibitors can promote the apoptosis of leukemia cells and increase their sensitivity to NK cells.
