title: Antibiotic drug tigecycline reduces neuroblastoma cells proliferation by inhibiting Akt activation in vitro and in vivo.
abstract: As the first member of glycylcycline bacteriostatic agents, tigecycline is approved as a novel expanded-spectrum antibiotic, which is clinically available. However, accumulating evidence indicated that tigecycline was provided with the potential application in cancer therapy. In this paper, tigecycline was shown to exert an anti-proliferative effect on neuroblastoma cell lines. Furthermore, it was found that tigecycline induced G1-phase cell cycle arrest instead of apoptosis by means of Akt pathway inhibition. In neuroblastoma cell lines, the Akt activator insulin-like growth factor-1 (hereafter referred to as IGF-1) reversed tigecycline-induced cell cycle arrest. Besides, tigecycline inhibited colony formation and suppressed neuroblastoma cells xenograft formation and growth. After tigecycline treatment in vivo, the Akt pathway inhibition was confirmed as well. Collectively, our data provided strong evidences that tigecycline inhibited neuroblastoma cells growth and proliferation through the Akt pathway inhibition in vitro and in vivo. In addition, these results were supported by previous studies concerning the application of tigecycline in human tumors treatment, suggesting that tigecycline might act as a potential candidate agent for neuroblastoma treatment.
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400715, People's Republic of China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400715, People's Republic of China.
authors.forename: Erhu
authors.initials: E
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400715, People's Republic of China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400715, People's Republic of China.
authors.forename: Weibo
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400715, People's Republic of China.|Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400715, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Cancer Center, Medical College of Georgia, Georgia Regents University, Augusta, GA, 30912, USA.
authors.forename: Han-Fei
authors.initials: HF
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400715, People's Republic of China. hongjuan.cui@gmail.com.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Cui
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000078304:Tigecycline; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000900:Anti-Bacterial Agents; D014408:Biomarkers, Tumor; D007334:Insulin-Like Growth Factor I; D000078304:Tigecycline; D051057:Proto-Oncogene Proteins c-akt; D008911:Minocycline
keywords: Akt activation; Cell cycle arrest; Cell proliferation; Neuroblastoma; Tigecycline