Plasmocytes tumoraux et autophagie

Lamy, Laurence

doi:10.1051/medsci/2013298002

Cited by 2 publications

(1 citation statement)

References 11 publications

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“…Research on autophagy in MM drug resistance is a hot topic [ 29 , 30 ], and DEPTOR also induces MM drug resistance through autophagy [ 31 – 33 ]. Many previous studies have shown that endogenous HMGB1 can induce drug resistance through autophagy [ 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

HMGB1 knockdown increases MM cell vulnerability by regulating autophagy and DNA damage repair

Guo

Zhang

et al. 2018

J Exp Clin Cancer Res

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BackgroundWith the development of novel therapeutic agents, the survival of multiple myeloma (MM) patients has much improved. However, the disease is incurable due to drug resistance. Previous studies have found that high-mobility group box 1 (HMGB1) is involved in inflammation, angiogenesis, DNA damage repair, and cancer invasion, progression, metastasis and drug resistance and that high HMGB1 expression is associated with poor MM prognosis, yet the role and mechanism of HMGB1 in MM remains unclear.MethodsThrough gene expression and Oncomine database analyses, we found that HMGB1 is associated with a poor prognosis in MM patients. RNA interference together with gene array analysis, cell proliferation and apoptosis assays, autophagy detection assays, western blotting, and in vivo xenograft models were employed to evaluate the effect of HMGB1 and the mechanism involved in MM drug resistance.ResultsMM cell lines and primary MM samples were found to express high levels of HMGB1, which was negatively associated with the 3-year survival of MM patients. HMGB1 knockdown in MM cells enhanced the inhibitory effect of chemotherapy with dexamethasone (Dex) via apoptosis induction. Furthermore, downregulation of HMGB1 activated the mTOR pathway, inhibited autophagy and increased DNA damage induced by Dex by modulating expression of related genes. In vivo, xenograft models showed that after Dex treatment, the tumor burden of HMGB1-knockdown mice was decreased compared with that of control mice.ConclusionsOur research shows that HMGB1 participates in autophagy and DNA damage repair and that downregulation of HMGB1 enhances the sensitivity of MM cells to Dex, suggesting that HMGB1 may serve as a target for MM treatment.

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