Influence of HMGB1/MAPK/m-TOR signaling pathway on cell autophagy and chemotherapy resistance in K562 cells.
- Author:
Liying LIU
1
;
Fei GAO
1
;
Yanqiong YE
2
;
Zhiheng CHEN
3
;
Yunpeng DAI
1
;
Ping ZHAO
1
;
Guotao GUAN
1
;
Mingyi ZHAO
3
Author Information
1. Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shangdong University, Jinan 250021, China.
2. Department of Cardiac Surgery, Guangdong General Hospital, Guangzhou 510010, China.
3. Department of Pediatrics, Third Xiangya Hospital, Central South University, Changsha 410013, China.
- Publication Type:Journal Article
- MeSH:
AMP-Activated Protein Kinases;
genetics;
physiology;
Arsenic Trioxide;
Arsenicals;
Autophagy;
genetics;
Cytarabine;
Doxorubicin;
Drug Resistance, Neoplasm;
genetics;
physiology;
Etoposide;
HMGB1 Protein;
genetics;
physiology;
Humans;
K562 Cells;
physiology;
Microtubule-Associated Proteins;
Oxides;
RNA, Small Interfering;
Signal Transduction;
TOR Serine-Threonine Kinases;
genetics;
physiology;
Vincristine
- From:
Journal of Central South University(Medical Sciences)
2016;41(10):1016-1023
- CountryChina
- Language:Chinese
-
Abstract:
To observe the effect of high-mobility group box 1 (HMGB1) on autophagy and chemotherapy resistance in human leukemiacell line (K562) cells, and to explore the underlying mechanisms.
Methods: The K562 cells were cultured in vitro and divided into 6 groups: a chemotherapeutic group, a chemotherapeutic control group, a HMGB1 preconditioning group, a HMGB1 preconditioning control group, a HMGB1 siRNA group and a siRNA control group. The chemotherapeutic group was further divided into a vincristine (VCR) group, an etoposide (VP-16) group, a cytosine arabinoside (Ara-C) group, a adriamycin (ADM) group and a arsenic trioxide (As2O3) group. The cell activity was evaluated by cell counting kit-8. The protein levels of HMGB1, microtubule-associate protein1light chain3 (LC3), AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (m-TOR) were determined by Western blotting. The level of serum HMGB1 was evaluated by enzyme-linked immunosorbent assay (ELISA). The autophagy was examined by monodansylcadaverine staining and observed under transmission electron microscopy.
Results: Compared with the control group, the cell activity was significantly decreased and the level of serum HMGB1 was significantly increased in the chemotherapeutic (VCR, VP-16, Ara-C, ADM and As2O3) groups (all P<0.05). Compared with the control group, the cell activity and the level of serum HMGB1 were significantly increased in the HMGB1 preconditioning group (both P<0.05). Compared with the siRNA control group, the cell activity and the level of serum HMGB1 were significantly decreased in the HMGB1 siRNA group (both P<0.05). Compared with the control group, the expression of LC3-II and the formation of autophagic bodies were increased in the HMGB1 preconditioning group (both P<0.05), the p-AMPK expression was increased and p-mTOR expression was decreased (both P<0.05).
Conclusion: HMGB1 can increase the autophagy and promote chemotherapy resistance through the pathway of AMPK/m-TOR in K562 cells.
