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Oxaliplatin Induces Immunogenic Cell Death in Human and Murine Laryngeal Cancer

BACKGROUND: Cisplatin resistance is observed in patients with laryngeal cancer. The present study was designed to explore the efficacy of oxaliplatin on laryngeal cancer and elucidate the underlying mechanisms. METHODS: Cell viability was determined by using MTT assays. Cell apoptosis was determined...

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Detalles Bibliográficos
Autores principales: Wang, Jingmiao, Zhang, Haizhong, Yin, Xiaoyan, Bian, Yanrui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484908/
https://www.ncbi.nlm.nih.gov/pubmed/36131787
http://dx.doi.org/10.1155/2022/3760766
Descripción
Sumario:BACKGROUND: Cisplatin resistance is observed in patients with laryngeal cancer. The present study was designed to explore the efficacy of oxaliplatin on laryngeal cancer and elucidate the underlying mechanisms. METHODS: Cell viability was determined by using MTT assays. Cell apoptosis was determined by using annexin V and propidium iodide (PI) staining. Flow cytometry and immunofluorescence were applied to determine the levels of calreticulin (CALR) and DiD (1,1-dioctadecyl-3,3,3,3-tetramethylindodicarbocyanine). Flow cytometry was applied to analyze the levels of CD83, CD86, IFN-γ-producing CD8(+) T cells, and CD4(+)CD25(+)FoxP3(+) Tregs. The levels of adenosine triphosphate (ATP) were determined by using a chemiluminescent ATP kit and cytokines were determined by using specific enzyme-linked immunosorbent assays (ELISAs). The levels of HMGB1 were determined by using Western blot and ELISA, respectively. The xenograft animal model was constructed to evaluate the antitumor effects of oxaliplatin. RESULTS: Oxaliplatin inhibited cell growth, promoted cell apoptosis, and induced the levels of CALR, ATP, and high mobility group box protein 1 (HMGB1) in Hep-2 cells. Oxaliplatin-treated Hep-2 cells increased the intensity of DiD and the levels of CD83 and CD86 in dendritic cells (DCs), as well as induced the supernatant IL-6 and TNF-α. Oxaliplatin-treated primary laryngeal cancer cell-pulsed DCs increased the IFN-γ-producing CD8(+) T cells and suppressed CD4(+)CD25(+)FoxP3(+) Tregs. In vivo data showed that oxaliplatin suppressed tumor growth and increased the populations of CD86(+)CD80(+) and CD8(+)CD45(+) cells in the tumor tissues. CONCLUSION: Treatment with oxaliplatin inhibited laryngeal cancer cells by inducing immunogenic cell death.