[Influence of HMGB1/MAPK/m-TOR signaling pathway on cell autophagy and chemotherapy resistance in K562 cells].
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.
Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shangdong University, Jinan 250021, China.
Liying
L
Liu
Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shangdong University, Jinan 250021, China.
Fei
F
Gao
Department of Cardiac Surgery, Guangdong General Hospital, Guangzhou 510010, China.
Yanqiong
Y
Ye
Department of Pediatrics, Third Xiangya Hospital, Central South University, Changsha 410013, China.
Zhiheng
Z
Chen
Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shangdong University, Jinan 250021, China.
Yunpeng
Y
Dai
Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shangdong University, Jinan 250021, China.
Ping
P
Zhao
Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shangdong University, Jinan 250021, China.
Guotao
G
Guan
Department of Pediatrics, Third Xiangya Hospital, Central South University, Changsha 410013, China.
Mingyi
M
Zhao
D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000502:physiology*; D000077237:Arsenic Trioxide; D001152:Arsenicals; D001343:Autophagy / Q000235:genetics*; D003561:Cytarabine; D004317:Doxorubicin; D019008:Drug Resistance, Neoplasm / Q000235:genetics* / Q000502:physiology*; D005047:Etoposide; D024243:HMGB1 Protein / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D020014:K562 Cells / Q000502:physiology; D008869:Microtubule-Associated Proteins; D010087:Oxides; D034741:RNA, Small Interfering; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000502:physiology*; D014750:Vincristine
D001152:Arsenicals; D024243:HMGB1 Protein; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D010087:Oxides; D034741:RNA, Small Interfering; D003561:Cytarabine; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000077237:Arsenic Trioxide