Deparment of Nutrition and Food Hygiene, School of Public Health, Suzhou Medical College of Soochow University, Suzhou 215123, China.
Deparment of Nutrition and Food Hygiene, School of Public Health, Suzhou Medical College of Soochow University, Suzhou 215123, China; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Beijing 100037, China.
Steroids. 2024 Nov;211:109488. doi: 10.1016/j.steroids.2024.109488. Epub 2024 Aug 14.
Several studies have indicated that 1α,25-hydroxyvitamin D [1α,25(OH)D] inhibits the proliferation and metastasis of cancer cells through suppressing epithelial-mesenchymal transition. However, its influence on the translocation of β-catenin remains unclear. In the present study, ovarian cancer stem-like cells (CSCs), including side population (SP) and CD44/CD117, were isolated from mouse ovarian surface epithelial (MOSE) cells with malignant transformation. The findings revealed that 1α,25(OH)D obviously reduced the sphere-forming ability, as well as Notch1 and Klf levels. Moreover, the limiting dilution assay demonstrated that 1α,25(OH)D effectively hindered the tumorigenesis of ovarian CSCs in vitro. Notably, treatment with 1α,25(OH)D led to a substantial increase in the cell population of CD44/CD117 forming one tumor from ≤ 100 to 445 in orthotopic transplanted model, indicating a pronounced suppression of stemness of ovarian CSCs. Additionally, 1α,25(OH)D robustly promoted the translocation of β-catenin from the nuclear to the cytoplasm through directly binding to VDR, which resulted in decreased levels of c-Myc and CyclinD1 within late MOSE cells. Taken together, these results strongly supported the role of 1α,25(OH)D in inhibiting stem-like properties in ovarian cancer cells by restraining nuclear translocation of β-catenin, thereby offering a promising target for cancer therapeutics.
已有多项研究表明，1α,25-二羟维生素 D [1α,25(OH)D] 通过抑制上皮间质转化来抑制癌细胞的增殖和转移。然而，其对β-连环蛋白易位的影响尚不清楚。在本研究中，从具有恶性转化的小鼠卵巢表面上皮（MOSE）细胞中分离出卵巢癌干细胞样细胞（CSC），包括侧群（SP）和 CD44/CD117。研究结果表明，1α,25(OH)D 明显降低了球体形成能力以及 Notch1 和 Klf 的水平。此外，有限稀释分析表明，1α,25(OH)D 有效地抑制了卵巢 CSC 的体外致瘤性。值得注意的是，用 1α,25(OH)D 处理后，CD44/CD117 形成一个肿瘤的细胞群体从≤100 个显著增加到 445 个，在原位移植模型中，表明卵巢 CSC 的干性显著受到抑制。此外，1α,25(OH)D 通过直接与 VDR 结合，强烈促进β-连环蛋白从核内易位到细胞质，导致晚期 MOSE 细胞中 c-Myc 和 CyclinD1 的水平降低。综上所述，这些结果有力地支持了 1α,25(OH)D 通过抑制β-连环蛋白的核易位来抑制卵巢癌细胞的类干细胞特性的作用，为癌症治疗提供了一个有前途的靶点。
