IL-1β调控口腔鳞癌代谢重编程的模式及机制研究

代谢重编程 (metabolic reprogramming)是恶性肿瘤发生发展重要机制之一，干预代谢重编程有望成为肿瘤防治的新策略。目前发现口腔鳞癌（oral squamous cell carcinoma，OSCC）也发生代谢重编程，但其机制及转化研究尚未深入。我们近期发现：作为口腔黏膜上皮细胞恶性转化过程的关键节点，IL-1β可引起OSCC细胞培养上清乳酸含量增加、葡萄糖浓度下降，并呈剂量依赖性。由于乳酸是肿瘤代谢重编程的终产物和效应物、与头颈部鳞癌预后负相关，我们假设：IL-1β可能通过上调AKT等关键基因上调乳酸产生、蓄积与分泌，以IL-1β－乳酸双向正反馈模式调控OSCC代谢重编程。为此，本项目拟开展IL-1β－乳酸双向正反馈模式调控OSCC代谢重编程机制的体内外实验研究，以期阐明OSCC代谢重编程的调控机制和意义，为开展OSCC基于肿瘤代谢重编程的转化研究提供理论与实验基础。

Metabolic reprogramming is a key energy metabolic hallmark of cancer, which confers a selective advantage for survival and proliferation in the unique tumor microenvironment, correlating closely with tumorigenesis, development, progression and clinical outcome of cancer. Recently,we found that IL-1β, as one of the key nodes of regulating network during malignant transformation of oral mucosa, enhanced efficiently the glucose utilization and lactate concentration of the cell lines supernatant of oral squamous cell carcinoma (OSCC) in a dose-depentdent manner. Since the lactate is a metabolic key player in cancer and high tumor lactate concentrations are correlated with poor prognosis of OSCC patients, we hypothesize that IL-1β play a central role in regulation of OSCC metabolic reprogramming by a pattern of IL-1β-lactate positive feedback loop. Therefore, the aim of this innovate research is to disclose the mechanisms of IL-1β-lactate positive feedback loop in regulation of OSCC metabolic reprogramming by the in vitro and in vivo studies of OSCC cell lines, model animals and clinical samples so as to give new lights into the metabolic reprogramming-based translational strategies of oral carcinogenesis.