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Neuroblastoma (NB) is one of the most common tumors in childhood. Unfortunately, the survival outcomes remain unsatisfactory since NB commonly develops multidrug resistance. Recent studies have demonstrated that the high mobility group box 1 (HMGB1)-mediated autophagy promotes chemoresistance in osteosarcoma, lung adenocarcinoma and ovarian cancer, but the exact molecular mechanism underlying HMGB1-mediated autophagy in NB has not been clearly defined. In the present study, we investigated the role of HMGB1 in the development of resistance to anticancer agents in NB. Anticancer agents including doxorubicin, cisplatin and etoposide each induced HMGB1 upregulation, promoted cytosolic HMGB1 translocation and the elevation of autophagic activity in human NB cells. RNA interference-mediated knockdown of HMGB1 restored the chemosensitivity of NB cells. Furthermore, mechanistic investigation revealed that HMGB1 promoted the proliferative activity and invasive potential of NB cells. HMGB1 enhanced drug resistance by inducing Beclin-1-mediated autophagy, an intracellular self-defense mechanism known to confer drug resistance. In addition, we found that HMGB1 facilitated autophagic progression and reduced oxidative stress induced by doxorubicin. Therefore, through its role as a regulator of autophagy, HMGB1 is a critical factor in the development of chemoresistance and tumorigenesis, and it may be a novel target for improving the efficacy of NB therapy.

Background: Interleukin-10 is an important cytokine that regulates immune response. Previous studies have shown that human cytomegalovirus can trigger cell autophagy during the early stages of infection. To our knowledge, whether IL-10 inhibits HCMV-induced autophagy and virus replication has not been studied previously., Objectives: We investigated whether IL-10 affects cell viability and autophagy under the conditions of starvation and HCMV infection by using the MRC5 cell line. We also explored the role of IL-10-mediated autophagy on HCMV replication., Results: Our data showed that IL-10 inhibited the autophagic flux of the MRC5 cells irrespective of starvation or HCMV infection, and suppressed HCMV replication. The promotion of autophagy with either a pharmacological inducer (rapamycin), or a technique to over-express the BECN1 gene reversed the effect of IL-10 on virus replication. Furthermore, the PI3K/Akt signal pathway was activated when the cells were pretreated with IL-10., Conclusions: Our results indicated that IL-10 can suppress HCMV replication by inhibiting autophagy in host cells during the early stages of infection., (Copyright © 2014 Elsevier Inc. All rights reserved.)