背景：胃癌是全世界最常见的胃肠道癌症。最新数据显示，它是癌症相关死亡的第四大原因。症状不明显、早期诊断困难，很大程度上影响治疗效果。因此，研究胃癌的相关基因和信号转导通路就显得尤为重要。我们前期研究发现维生素D受体（VDR）基因FokI多态性可能与中国汉族人群胃癌易感性相关。然而，VDR影响胃癌的机制尚不清楚。在本研究中，我们探讨了VDR调节胃癌发生和进展的分子机制和可能的信号通路。方法：采用质粒转染和RNA干扰技术干扰胃癌细胞系中VDR的表达。然后通过MTT实验、集落形成实验、Transwell迁移实验分析细胞活力和侵袭能力，并通过SDS-PAGE和Western blotting检测胃癌细胞中VDR和多种信号蛋白的表达。结果：VDR过表达能够显着抑制胃癌细胞的生存能力和侵袭能力；相反，当VDR siRNA抑制VDR的表达时，胃癌细胞的活力和侵袭能力增强。经1,25(OH)2D3处理的胃癌细胞中VDR表达水平呈现时间依赖性表达增加；随着VDR表达量的增加，β-catenin的表达量逐渐下降，而E-cadherin的表达量呈时间依赖性增加（P < 0.05）。与突变型VDR基因(ff)细胞相比，转染纯合野生型VDR基因(FF)质粒后β-catenin下降程度显着增强(p<0.05)。结论：本研究结果提示VDR FokI多态性在胃癌细胞的增殖、侵袭、克隆形成等恶性表型中发挥重要作用。当VDR被其配体激活后，可阻止β-catenin入核，影响E-cadherin水平，抑制胃癌细胞的增殖，提示VDR FokI基因可能通过Wnt发挥抑癌作用/β-连环蛋白信号通路。© 作者。

Background: Gastric cancer is the most common gastrointestinal cancer worldwide. The latest data showed that it was the fourth leading cause of cancer-related death. The unobvious symptom and the difficulties lying in the early diagnosis largely affect the effect of the treatment. Therefore, it becomes particularly important to investigate the related genes and signal transduction pathways in gastric cancer. Our previous study found that the vitamin D receptor (VDR) gene FokI polymorphism may be associated with susceptibility to gastric cancer in the Chinese Han population. However, the mechanism of VDR affecting gastric cancer is unknown. In this study, we explored the molecular mechanism and the possible signaling pathway of VDR modulating carcinogenesis and progression of gastric cancer. Methods: The expression of VDR in gastric cancer cell lines was interfered by plasmid transfection and RNA interference technology. And then we analyzed the cell viability and invasive ability by MTT assay, colony formation assay, and transwell migration assay, and detected the expression of VDR and several signaling proteins in gastric cancer cells by SDS-PAGE and Western blotting. Results: The overexpression of VDR can significantly inhibit the viability and invasive ability of gastric cancer cells; on the contrary, when VDR siRNA inhibits the expression of VDR, the viability and invasive ability of gastric cancer cells enhanced. VDR expression levels in gastric cancer cells treated with 1,25 (OH) 2D3 showed a time-dependent increased expression; and with the increase of the VDR expression, the expression of β-catenin decreased gradually, but the expression of E-cadherin showed a time-dependent increase (P < 0.05). Compared with the mutant-type VDR gene(ff) cells, the degree of β-catenin decline was significantly enhanced after transfected with homozygous wild-type VDR gene (FF) plasmids (p<0.05). Conclusions: The results of this study indicate that VDR FokI polymorphism plays an important role in the malignant phenotype of gastric cancer cells, such as proliferation, invasion, and clone formation. When the VDR is activated by its ligand, it can prevent the nuclear import of β-catenin, affect the E-cadherin level, inhibit the proliferation of gastric cancer cells, which suggested that VDR FokI gene may play a role of cancer suppressor via Wnt/β-catenin signaling pathway.© The author(s).