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Article

Trichostatin A reduces cisplatin-induced ototoxicity through the STAT6 signaling pathway

  • Authors:
    • Ji Huang
    • Ping Wang
    • Min Li
    • Jingyan Ge
    • Jiaqi Chen
    • Xia Chen
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, P.R. China, Department of Otolaryngology-Head and Neck Surgery, The First Hospital of Jilin University, Changchun, Jilin, P.R. China, Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, P.R. China
  • Pages: 493-500
    |
    Published online on: June 16, 2015
       https://doi.org/10.3892/ijmm.2015.2249
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Abstract

Cisplatin-induced ototoxicity limits its wide application in the treatment of cancer. A number of pro-inflammatory factors have been shown to be involved in cisplatin-induced ototoxicity. Trichostatin A (TSA) is an anti-inflammatory agent that has been shown to exert protective effects against cisplatin-induced ototoxicity. In the present study, we hypothesized that TSA may protect cochlear hair cells from cisplatin-induced damage by regulating the interleukin (IL)-4/signal transducer and activator of transcription (STAT)6 signaling pathway. Wistar rat cochlear explants were cultured in DMEM. The differentially expressed genes of the basilar membrane were identified by microarray analysis of global expression profiles. Hair cells were stained with rhodamine phalloidin and observed under a scanning electron microscope to evaluate the protective effects of TSA against cisplatin-induced cochlear hair cell damage. The levels of cytokines in the supernatant of the cultured basilar membranes was measured using ELISA. STAT6 and phosphorylated (p-)STAT6 expression was measured by western blot analysis. Morphological observation revealed that cisplatin induced the disarrangement of the cochlear hair cells, as well as the fusion and detachment of the cilia, while these aberrant alterations were inhibited by TSA, suggesting that TSA exerts a protective effect against cisplatin-induced damage to hair cells. Furthermore, the increase in the expression of STAT6 and p-STAT6 induced by cisplatin was reversed by treatment with TSA, accompanied by the decreased expression of IL-1β, IL-4 and IL-6. Therefore, our data demonstrate that TSA reduces cisplatin-induced ototoxicity by inhibiting pro-inflammatory factor-mediated STAT6 signaling. Thus, TSA may be used to prevent the side-effects associated with the use of cisplatin in cancer treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Huang J, Wang P, Li M, Ge J, Chen J and Chen X: Trichostatin A reduces cisplatin-induced ototoxicity through the STAT6 signaling pathway. Int J Mol Med 36: 493-500, 2015.
APA
Huang, J., Wang, P., Li, M., Ge, J., Chen, J., & Chen, X. (2015). Trichostatin A reduces cisplatin-induced ototoxicity through the STAT6 signaling pathway. International Journal of Molecular Medicine, 36, 493-500. https://doi.org/10.3892/ijmm.2015.2249
MLA
Huang, J., Wang, P., Li, M., Ge, J., Chen, J., Chen, X."Trichostatin A reduces cisplatin-induced ototoxicity through the STAT6 signaling pathway". International Journal of Molecular Medicine 36.2 (2015): 493-500.
Chicago
Huang, J., Wang, P., Li, M., Ge, J., Chen, J., Chen, X."Trichostatin A reduces cisplatin-induced ototoxicity through the STAT6 signaling pathway". International Journal of Molecular Medicine 36, no. 2 (2015): 493-500. https://doi.org/10.3892/ijmm.2015.2249
Copy and paste a formatted citation
x
Spandidos Publications style
Huang J, Wang P, Li M, Ge J, Chen J and Chen X: Trichostatin A reduces cisplatin-induced ototoxicity through the STAT6 signaling pathway. Int J Mol Med 36: 493-500, 2015.
APA
Huang, J., Wang, P., Li, M., Ge, J., Chen, J., & Chen, X. (2015). Trichostatin A reduces cisplatin-induced ototoxicity through the STAT6 signaling pathway. International Journal of Molecular Medicine, 36, 493-500. https://doi.org/10.3892/ijmm.2015.2249
MLA
Huang, J., Wang, P., Li, M., Ge, J., Chen, J., Chen, X."Trichostatin A reduces cisplatin-induced ototoxicity through the STAT6 signaling pathway". International Journal of Molecular Medicine 36.2 (2015): 493-500.
Chicago
Huang, J., Wang, P., Li, M., Ge, J., Chen, J., Chen, X."Trichostatin A reduces cisplatin-induced ototoxicity through the STAT6 signaling pathway". International Journal of Molecular Medicine 36, no. 2 (2015): 493-500. https://doi.org/10.3892/ijmm.2015.2249
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