天然虾青素在食管鳞癌预防中的作用及其相关机制研究

Esophageal carcinoma is one of the most common malignant tumors posing a threat to the health of Chinese population. How to reduce the incidence and mortality of esophageal cancer is an important problem of public health for the medical researchers. Many kinds of carotenoids have been proved to have protective effect of the occurrence of esophageal carcinoma and can reduce the risk of esophageal cancer in vitro and in vivo. Astaxanthin is the terminal metabolite of the biosynthesis of carotenoid form and the powerful antioxidant with significant anti-tumor activity properties for a wide variety of tumor. However, the inhibitory effects of astaxanthin on the esophageal squamous carcinoma and its possible mechanisms have not yet been studied. In this study, the effect of astaxanthin on proliferation and apoptosis of esophageal squamous cancer cells will be investigated using cell culture in vitro. Molecular biological technique will be used to identify whether astaxanthin is one natural PPARγ ligand which can activated PPAR γ, and then affect the transcription of NF-κB and other downstream genes. Animal model of esophageal squamous carcinoma will be established to investigate the inhibitory effect of astaxanthin supplementary in the process of esophageal epithelial cells canceration. Inhibitory effects and its underlying mechanisms of chemoprevention to esophageal squamous cell carcinoma will be clarified from different levels. Results will provide theoretical basis for the chemoprevention and therapy of esophageal squamous cell carcinoma and other diseases.

食管癌是严重威胁我国人民健康的恶性肿瘤之一，如何降低人群食管癌的发病率和病死率，是医学科研工作者面临的一项重要公共卫生问题。体内外研究证实多种类胡萝卜素对食管癌的发生具有一定保护作用，能够降低食管癌的发病风险。虾青素是类胡萝卜素生物合成的终端形态，是一种超级抗氧化剂，具有抗多种肿瘤细胞的活性，但是关于虾青素对食管鳞癌的抑制效果及相关机制尚未见研究。本课题拟通过体外细胞培养，观察虾青素对食管鳞癌细胞增殖和凋亡的影响；通过分子生物学手段研究虾青素是否作为PPARγ配体活化PPARγ分子，进而影响NF-κB及其他下游目的基因的转录；通过食管鳞癌动物模型，在整体水平上研究虾青素干预在食管上皮癌变过程中抑制作用，从多个层面阐明天然虾青素在预防食管鳞癌中的作用及相关分子机制。研究结果将为食管鳞癌及其他疾病预防和治疗提供新的研究思路和理论依据

食管癌是严重威胁我国人民健康的恶性肿瘤之一，食管癌与营养的关系密切相关，通过营养素干预降低食管癌的发生显得尤为重要。本项目通过N-甲基苄基亚硝胺（N-nitrosomethylbenzylamine, NMBzA）构建F344大鼠食管癌模型，不同浓度虾青素，不同阶段干预F344大鼠，观察虾青素干预食管癌的效果及相关机制。结果显示，虾青素适当剂量虾青素油剂能够抑制NMBzA诱导的大鼠食管癌发生，可能通过提高大鼠抗氧化能力，抑制核转录因子(NF-κB)水平，提高大鼠TGF-β1的水平，达到抑制食管癌的发生。