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
,
3
;
Wei XU
4
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
3. 2Changzhou No.3 People's Hospital, Changzhou 213000, Jiangsu Province, China.
4. 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.
