IFIT2在头颈部鳞癌mitoxantrone耐药过程中的机制研究

Mitoxantrone has strong anti-tumor effect and minimal side effect, with good prospect in head and neck cancer. However, mitoxantrone is prone to drug resistance in head and neck cancer, and its resistance mechanism is unclear. Combined RNA-seq database of head and neck cancer cells with drug susceptibility test, we found that IFIT2 expression was closely related to mitoxantrone resistance in head and neck cancer and IFIT2 was correlated with the expression of TNF-α and its downstream BCL2, and TNF-α could regulate mitoxantrone resistance. In summary, we speculate that IFIT2 may be important to mitoxantrone resistance in head and neck cancer, and can regulate TNF-α-related apoptosis signaling pathways affecting resistance to mitoxantrone in head and neck cancer. Therefore, the project intends to study how IFIT2 regulate TNF-α and its apoptosis-related signaling pathways downstream at cellular level, and validate in animal models and clinical tumor samples, in order to clarify how IFIT2 induce mitoxantrone-resistant in head and neck cancer and provide the theoretical basis for the clinical application of mitoxantrone in head and neck cancer.

Mitoxantrone具有较强的抗肿瘤作用，且毒副作用小，在头颈癌中具有很好的应用前景。但是，mitoxantrone在头颈癌中容易产生耐药，其耐药机制尚不清楚。课题组结合头颈癌细胞RNA-seq数据库和药敏检测，分析发现IFIT2表达水平与头颈癌mitoxantrone耐药密切相关，且IFIT2与TNF-α及其下游BCL2的表达具有相关性，而TNF-α可调控mitoxantrone耐药。综上，我们推测IFIT2可能是头颈癌mitoxantrone耐药的重要基因，可调控TNF-α相关细胞凋亡信号通路，从而影响头颈癌mitoxantrone的耐药性。因此，本项目拟在细胞水平研究IFIT2调控TNF-α及其下游细胞凋亡相关信号通路的机制，并在动物模型和临床肿瘤样本中验证，以期阐明IFIT2诱导头颈癌mitoxantrone耐药的机制，为mitoxantrone在头颈癌的临床应用提供理论依据。