Mechanisms of aspirin-induced apoptosis in EBV-transformed human B lymphocytes
10.3969/j.issn.1001-1978.2017.02.009
- VernacularTitle:阿司匹林诱导EB病毒转化的人B淋巴细胞凋亡
- Author:
Yufen TAO
;
Bo LIU
;
Chao LI
;
Xintong LI
;
Jiansheng LIU
;
Zhaoqing YANG
;
Hongqi LIU
- Keywords:
aspirin;
EBV-transformed human B-lym-phocytes;
apoptosis;
mTOR;
PU.1 -Bim axis;
anti-tumor
- From:
Chinese Pharmacological Bulletin
2017;33(2):185-190
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the effects of aspirin on Epstein-Barr virus (EBV)-transformed human B-lym-phocytes.Methods EBV-transformed human B-lym-phocytes were treated with certain concentrations of as-pirin.Cellular proliferation was analyzed by MTT as-say.Further evaluation of apoptosis of aspirin-treated cells was performed through light-field microscope, transmission electronic microscope(TEM),propidium iodide(PI)staining and flow cytometric analysis and DNA electrophoresis. Finally, immunoblot analysis was used to determine the expression levels of apopto-sis-associated proteins, proteins involved in mTOR pathway and PU.1 -Bim axis.Results Aspirin treat-ment inhibited proliferation of EBV-transformed human B-lymphocytes.We observed that aspirin treatment in-duced apoptosis in EBV-transformed human B-lympho-cytes,resulting in the decreased number and size of cells.Ultramicroscopic structural analysis via TEM in-dicated that aspirin treatment deformed the cellular nu-cleus,and led to peripheral chromatin and cytoplasmic vacuole.PI staining and flow cytometric analysis indi-cated that aspirin increased the permeability of cell membrane and decreased the viability of treated cells. Agarose electrophoresis revealed DNA smear in aspirin-treated cells.Mechanistically,mTOR signaling was in-hibited in aspirin-treated cells,as evidenced by the de-creased phosphorylation of S6K1 and S6 via immunob-lot analysis.Aspirin treatment led to the decrease of hematopoietic transcription factor PU.1 .Consequently, pro-apoptotic Bim, apoptosis-associated proteins caspase-3 and PARP were activated in aspirin-treated cells.Conclusion Aspirin may show anti-lymphoma effects via its inhibition of proliferation and induction of apoptosis of EBV-transformed human B-lymphocytes, in which mTOR signal pathway and PU.1 -Bim axis may be involved.
