INF-γ sensitizes head and neck squamous cell carcinoma cells to chemotherapy-induced apoptosis and necroptosis through up-regulation of Egr-1.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Acquired resistance to standard chemotherapy accounts for most of treatment failure. Here we demonstrate that Interferon-γ (INF-γ) may up-regulate Egr-1 gene expression in HNSCC cell line SCC-25. Forced expression of Egr-1 sensitizes SCC-25 cells to chemotherapy-induced apoptosis and necroptosis, a novel form of programmed cell death. Egr-1 up-regulation also significantly increases the production of Thrombospondin-1 (TSP-1), a matricellular glycoprotein which has been described to induce cell death in HNSCC. Moreover, INF-γ-induced sensitization of cells to chemotherapy-mediated cell death and TSP-1 production could be markedly abolished by Egr-1 silencing. The present investigation provides the first evidence that INF-γ may sensitize HNSCC cells to chemotherapy-induced apoptosis and necroptosis through up-regulation of Egr-1. These data support the combination use of INF-γ and cytotoxic drugs for HNSCC Therapy.
Department of Medical Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
Bei
B
Xu
Department of Medical Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China. shuyongqian@csco.org.cn.
Yongqian
Y
Shu
Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China. liupeng9098@163.com.
Peng
P
Liu
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D004357:Drug Synergism; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D005472:Fluorouracil / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009336:Necrosis; D000077195:Squamous Cell Carcinoma of Head and Neck; D019700:Thrombospondin 1 / Q000378:metabolism; D015854:Up-Regulation
D000970:Antineoplastic Agents; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D019700:Thrombospondin 1; D007371:Interferon-gamma; D002945:Cisplatin; D005472:Fluorouracil