title: TLR9-ERK-mTOR signaling is critical for autophagic cell death induced by CpG oligodeoxynucleotide 107 combined with irradiation in glioma cells.
abstract: Synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides (CpG ODN) function as potential radiosensitizers for glioma treatment, although the underlying mechanism is unclear. It was observed that CpG ODN107, when combined with irradiation, did not induce apoptosis. Herein, the effect of CpG ODN107 + irradiation on autophagy and the related signaling pathways was investigated. In vitro, CpG ODN107 + irradiation induced autophagosome formation, increased the ratio of LC3 II/LC3 I, beclin 1 and decreased p62 expression in U87 cells. Meanwhile, CpG ODN107 also increased LC3 II/LC3 I expression in U251 and CHG-5 cells. In vivo, CpG ODN107 combined with local radiotherapy induced autophagosome formation in orthotopic transplantation tumor. Investigation of the molecular mechanisms demonstrated that CpG ODN107 + irradiation increased the levels of TLR9 and p-ERK, and decreased the level of p-mTOR in glioma cells. Further, TLR9-specific siRNA could affect the expressions of p-ERK and autophagy-related proteins in glioma cells. Taken together, CpG ODN107 combined with irradiation could induce autophagic cell death, and this effect was closely related to the TLR9-ERK-mTOR signaling pathway in glioma cells, providing new insights into the investigation mechanism of CpG ODN.
authors.affiliation: Department of Pharmacology, College of Pharmacy, the Third Military Medical University, Chongqing 400038, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmacology, College of Pharmacy, the Third Military Medical University, Chongqing 400038, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Cen
authors.affiliation: Department of Pharmacy, Institute of Surgery Research, Daping Hospital, the Third Military Medical University, Chongqing 400042, China.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Pharmacology, College of Pharmacy, the Third Military Medical University, Chongqing 400038, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, College of Pharmacy, the Third Military Medical University, Chongqing 400038, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, College of Pharmacy, the Third Military Medical University, Chongqing 400038, China.
authors.forename: Guanqun
authors.initials: G
authors.lastname: Cao
authors.affiliation: Department of Pharmacology, College of Pharmacy, the Third Military Medical University, Chongqing 400038, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, College of Pharmacy, the Third Military Medical University, Chongqing 400038, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Pharmacology, College of Pharmacy, the Third Military Medical University, Chongqing 400038, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.affiliation: Company 18th, College of Pharmacy, the Third Military Medical University, Chongqing 400038, China.
authors.forename: Jintao
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Oncology, Southwest Hospital, the Third Military Medical University, Chongqing 400038, China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Pang
authors.affiliation: Medical Research Center, Southwestern Hospital, the Third Military Medical University, Chongqing 400038, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology, College of Pharmacy, the Third Military Medical University, Chongqing 400038, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001343:Autophagy; D001932:Brain Neoplasms / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000532:radiotherapy*; D006801:Humans; D020935:MAP Kinase Signaling System; D008819:Mice, Nude; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C576997:CpG ODN107; D009838:Oligodeoxyribonucleotides; D011838:Radiation-Sensitizing Agents; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases