Drug resistance has been recognized to be a major obstacle to the chemotherapy for osteosarcoma. Even when the importance of hypoxia to reverse drug resistance in osteosarcoma has been indicated, the mechanism underlining such role has not yet clarified. In the current study, we investigated the activation of high mobility group box 1 (HMGB1) signaling in osteosarcoma cells subject to anti-osteosarcoma drug, doxorubicin under hypoxia, and then utilized a HMGB1 inhibitor, glycyrrhizin, to block the activation of HMGB1 signaling, and then reevaluated the sensitivity of osteosarcoma cells to doxorubicin. It was demonstrated hypoxia reduces the viability reduction and apoptosis induction by doxorubicin in osteosarcoma U-O2S cells in vitro. And HMGB1 signaling is promoted in the doxorubicin-treated U-O2S cells under hypoxia. On the other side, the silence of HMGB1 receptor, also known as the receptor for advanced glycation endproducts (RAGE), sensitizes osteosarcoma U-O2S cells to doxorubicin under hypoxia. Moreover, glycyrrhizin, known as a HMGB1 inhibitor, regulates the sensitivity of osteosarcoma cells to doxorubicin under hypoxia. The present study confirmed the key mediation of role of HMGB1 signaling in the hypoxia-induced resistance to doxorubicin in osteosarcoma cells. And glycyrrhizin antagonize the drug-resistance to doxorubicin of osteosarcoma cells.
[1]Jilin Univ, China Japan Union Hosp, Dept Orthoped, Changchun 130033, Peoples R China.
[2]Jilin Univ, Hosp 2, Dept Ophthalmol, Changchun 130000, Peoples R China.
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