14-3-3ζ protein mediates gemcitabine resistance in NK/T-cell lymphoma.
10.3760/cma.j.issn.0253-2727.2019.11.004
- Author:
Ya Juan QIU
1
;
Ming Zhe ZHANG
Author Information
1. Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
- Publication Type:Journal Article
- Keywords:
Drug resistance;
Gemcitabine;
Lymphoma, extranodal NK/T-cell;
Protein 14-3-3ζ
- MeSH:
14-3-3 Proteins/metabolism*;
Cell Line, Tumor;
Deoxycytidine/therapeutic use*;
Drug Resistance, Neoplasm;
Humans;
Lymphoma, Extranodal NK-T-Cell/drug therapy*;
Gemcitabine
- From:
Chinese Journal of Hematology
2019;40(11):906-911
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the molecular mechanisms of 14-3-3ζ in gemcitabine resistance in extranodal NK/T-cell lymphoma, nasal type (ENKTL) . Methods: The effects of cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) assay and transwell assay. YTS cells were exposed to gradually increased concentrations of gemcitabine to establish gemcitabine-resistant YTS cells (YTS-gem) in vitro. 14-3-3ζ specific siRNA lentiviral vector was transfected into YTS and YTS-gem cells to downregulate 14-3-3ζ expression, and stable transfected cell clones were screened. The protein expression was determined by Western blot. Results: ①14-3-3ζ expression was significantly up-regulated in gemcitabine resistant YTS-gem cells, comparing with that of YTS cells (P<0.05) . ②The results of CCK-8 and transwell assay showed that downregulation of 14-3-3ζ significantly reduced the cell proliferation and invasion abilities (P<0.05) . ③Downregulation of 14-3-3ζ could restore gemcitabine sensitivity in gemcitabine resistant YTS-gem cells (P<0.05) . ④Western blotting results showed that knockdown of 14-3-3ζ significantly upregulated pro-apoptotic Bax, and downregulated anti-apoptotic Bcl-2, Caspase-3, cleaved caspase-3, Cyclin D1 in gemcitabine-resistant YTS-gem cells (P<0.05) . There was no significant difference in p53 ang P-gp expression levels. Conclusions: 14-3-3ζ was upregulated in gemcitabine resistant YTS cells. Overexpression of 14-3-3ζ promoted cell proliferation and enhanced cell migration. 14-3-3ζ contributed to gemcitabine resistance to ENKTL through anti-apoptosis.
