结肠癌是老年人常见的消化道肿瘤。流行病学证据显示活性维生素D 缺乏与衰老和结肠癌均有密切关系，提示在衰老进程中活性维生素D缺乏可能对结肠癌发病起着重要作用。我们前期研究发现活性维生素D缺乏的1α(OH)ase 基因敲除小鼠出现明显的机体衰老表型以及促进结肠移植瘤的形成和生长，我们推测活性维生素D的缺乏可能加速机体衰老进程进而促进结肠癌的发生和发展。为验证此假设，本项目将利用1α(OH)ase-/-小鼠建立VDR缺乏的结肠癌细胞移植瘤模型，从整体和细胞水平研究活性维生素D缺乏是否通过促使衰老相关分泌因子（如CCL20）的产生，进而促进结肠癌发生和发展；同时，研究活性维生素D补充是否能够改变1α(OH)ase-/-小鼠的衰老相关分泌表型，抑制移植瘤生长。研究结果将有助于揭示活性维生素D缺乏在衰老进程中促进结肠癌发生发展的作用机制及其在防治结肠癌中的作用机制，将为结肠癌的防治提供实验和理论依据。

Colon cancer is one of the most common gastrointestinal tumors of aged people. Epidemiological studies showed that 1,25(OH)2D3 insufficiency appears to be associated with aging and colon cancer, suggesting it plays a role in colon cancer initiation and development especially in older people. Our preliminary data showed that 1α (OH)ase knock-out mice (1α (OH)ase-/-) with the deficiency of 1,25(OH)2D3 display a typical aging phenotype including thin skin, weight loss, short life span, etc. Interestingly, the growth of xenografted CT-26.WT colon cancer cells was increased in 1α (OH)ase-/- mice. Based on results from previous studies and our preliminary data, we propose that 1,25(OH)2D3 deficiency may enhance colon cancer initiation and development during aging process. To test this hypothesis, the model of xenografted CT-26.WT colon cancer cells without VDR expression will be generated in 1α (OH)ase-/- mice and their wild-type littermates and assess whether 1,25(OH)2D3 deficiency could accelerate colon cancer initiation and development through increasing the production of senescence associated sectetory factors, such as CCL20. Simultaneously, we will use this model to assess whether the supplementation of exogenous 1,25(OH)2D3 could inhibit the growth of xenografted CT-26.WT colon cancer cells by altering senescence associated sectetory phenotype of 1α (OH)ase-/- mice. Results from this study will be helpful to clarify the mechanism of effect of 1,25(OH)2D3 deficiency on colon cancer initiation and development during aging and the mechanism of action of 1,25(OH)2D3 in colon cancer prevention and treatment, thus will provide experimental and theoretical basis for the application of 1,25(OH) 2D3 in colon cancer prevention and treatment.