title: HMGB1-mediated autophagy decreases sensitivity to oxymatrine in SW982 human synovial sarcoma cells.
abstract: Oxymatrine (OMT) is a type of alkaloid extracted from a traditional Chinese medicinal herb, Sophora flavescens. Although the antitumor activities of OMT have been observed in various cancers, there are no reports regarding the effects of OMT on human synovial sarcoma. In the present study, we analyzed the antitumor activities of OMT in SW982 human synovial sarcoma cells and determine whether high mobility group box protein 1 (HMGB1)-mediated autophagy was associated with its therapeutic effects. We found that OMT exhibited antitumor activity in SW982 cells and facilitated increases in autophagy. Inhibition of autophagy by 3-MA or ATG7 siRNA increased the level of apoptosis, which indicated that OMT-induced autophagy protected cells from the cytotoxicity of OMT. Administration of OMT to SW982 cells increased the expression of HMGB1. When HMGB1 was inhibited via HMGB1-siRNA, OMT-induced autophagy was decreased, and apoptosis was increased. Furthermore, we found that HMGB1-siRNA significantly increased the expression of p-Akt and p-mTOR. OMT-induced autophagy may be mediated by the Akt/mTOR pathway, and HMGB1 plays a vital role in the regulation of autophagy. Therefore, we believe that combining OMT with an inhibitor of autophagy or HMGB1 may make OMT more effective in the treatment of human synovial sarcoma.
authors.affiliation: Department of Orthopaedics of the First Affiliated Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.
authors.forename: Yongsong
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Joint Surgery, Xi'an Hong Hui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710054, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Joint Surgery, Xi'an Hong Hui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710054, China.
authors.forename: Le
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Joint Surgery, Xi'an Hong Hui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710054, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Joint Surgery, Xi'an Hong Hui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710054, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Joint Surgery, Xi'an Hong Hui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710054, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.
authors.forename: Congshan
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Orthopaedics of the First Affiliated Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.
authors.forename: Qiling
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Center for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Joint Surgery, Xi'an Hong Hui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710054, China.
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopaedics of the First Affiliated Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Qiu
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011807:Quinolizines / Q000494:pharmacology*; D013584:Sarcoma, Synovial / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D024243:HMGB1 Protein; D051057:Proto-Oncogene Proteins c-akt; D011807:Quinolizines; D058570:TOR Serine-Threonine Kinases; C585491:HMGB1 protein, human; C037573:oxymatrine; D000093842:Matrines; C546842:MTOR protein, human