title: Minocycline attenuates ototoxicity and enhances antitumor activity of cisplatin treatment in vitro.
abstract: OBJECTIVE
  Some agents have been shown to prevent cisplatin-induced ototoxicity. The objective is to show that the agent minocycline protects the cochlea against cisplatin damage and enhances the cytotoxicity of anticancer therapies.
  
  
  METHODS
  In vitro chemotherapeutic assessments of minocycline.
  
  
  METHODS
  Research laboratory.
  
  
  METHODS
  Hep-2 cells were cultured with and without 100 μM cisplatin, and cell growth inhibition was assessed. Autophagy in the samples was visually evaluated by electron microscopy and by beclin-1 expression using Western blotting. In another experiment, cochlear basilar membranes of 3-day-old rats were isolated and cultured. The cultures were treated with the same concentration of cisplatin or cisplatin combined with minocycline. Immunofluorescence staining was used to identify changes in spiral ganglions.
  
  
  RESULTS
  Cell growth was inhibited in a dose-dependent manner following minocycline treatment. Furthermore, the combination of cisplatin and minocycline effectively increased tumor cell death (P < .01). Autophagosomes were also evident in cells treated with minocycline. Beclin-l protein expression was increased after minocycline treatment in Hep-2 cells. In an experiment evaluating cochlear spiral ganglion neuron survival, it was found that the number of surviving cochlear neurons significantly increased in the minocycline pretreatment group compared with the group treated with cisplatin alone (P < .01).
  
  
  CONCLUSIONS
  This study shows that minocycline alone, or in combination with chemotherapeutic drugs, inhibits the growth of tumor cells and attenuates ototoxicity. It is also shown that minocycline activates cell autophagy via the beclin-1 signaling pathway, which may be an additional underlying cause of Hep- 2 cell death.
authors.affiliation: Department of Otolaryngology and Head & Neck Surgery, First Hospital, Jilin University, Changchun, Jilin, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Du
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001489:Basilar Membrane / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000009:adverse effects*; D004427:Ear Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D008911:Minocycline / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D046509:Tissue Culture Techniques; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D008911:Minocycline; D002945:Cisplatin