Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Endocr Metab Immune Disord Drug Targets. 2021;21(7):1312-1318. doi: 10.2174/1871530320666200821155756.
Osteosarcoma (OS) is the basic bone neoplasm with lower survival and poor prognosis. It is distinguished by its offensive nature and metastatic potential. The fundamental death source in OS patients is lung metastasis. In addition, the proliferation and cell migration are thus essential for cancer progression, especially for intrusion and transformation. Several studies have illustrated that 1,25-Dihydroxyvitamin D (1,25(OH)2D) has a critical role in the growth and differentiation of bone. However, knowledge of the outcome of 1,25(OH)2D on the progression and incursion of osteosarcoma cells is minimal.
The present study aimed to analyze the effect of different concentrations of 1,25(OH)2D on the multiplication, progression, and intrusion of OS cells and verify the effective doses of 1,25(OH)2D that can decrease the intensity of the disease and improving the prognosis in OS patients.
Saos-2 cells were treated with 1,25(OH)2D (0, 50, 100, and 200 nM) for 48, 72, and 96 hours. Proliferation, invasion, and migration were determined by MTT assay, Transwell assay, and Scratch test, respectively. The levels of c-Myc and FOXO1 proteins were determined by Western blotting.
The proliferation, invasiveness, and migration of Saos-2 cells that were treated with 1,25(OH)2D were significantly decreased compared with untreated cells. Although 1,25(OH)2D notably decreased c-Myc protein levels (after 48 and 72 hours), FOXO1 protein levels have been significantly increased after 48 and 72 hours. 1,25(OH)2D and the vitamin D receptor (VDR) suppress c-Myc function through regulating the c-Myc/MXD1 network and thus, providing a molecular basis of 1,25(OH)2D related to the cancer-preventive actions.
Based on the present results, 1,25(OH)2D by targeting c-Myc and FOXO1 expression displays anti-invasive, anti-migration and anti-proliferative effects on OS cells in vitro. Our findings suggest that effective doses of the 1,25(OH)2D may reduce the aggressive potential of the OS cell line. However, further investigation and clinical trials are needed.
骨肉瘤（OS）是一种基本的骨肿瘤，其生存率较低，预后较差。它的特点是侵袭性和转移性。OS 患者的基本死亡原因是肺转移。此外，增殖和细胞迁移对于癌症的进展至关重要，尤其是对于侵袭和转化。几项研究表明，1,25-二羟维生素 D（1,25（OH）2D）在骨的生长和分化中起着关键作用。然而，关于 1,25（OH）2D 对骨肉瘤细胞的进展和浸润的影响的知识还很有限。
本研究旨在分析不同浓度的 1,25（OH）2D 对 OS 细胞增殖、进展和浸润的影响，并验证能降低疾病强度和改善 OS 患者预后的有效 1,25（OH）2D 剂量。
用 1,25（OH）2D（0、50、100 和 200 nM）处理 Saos-2 细胞 48、72 和 96 小时。用 MTT 测定法、Transwell 测定法和划痕试验分别测定增殖、侵袭和迁移。用 Western blot 法测定 c-Myc 和 FOXO1 蛋白水平。
用 1,25（OH）2D 处理的 Saos-2 细胞的增殖、侵袭和迁移能力明显低于未处理的细胞。虽然 1,25（OH）2D 明显降低了 c-Myc 蛋白水平（48 和 72 小时后），但 FOXO1 蛋白水平在 48 和 72 小时后显著升高。1,25（OH）2D 和维生素 D 受体（VDR）通过调节 c-Myc/MXD1 网络抑制 c-Myc 功能，为 1,25（OH）2D 与癌症预防作用相关提供了分子基础。
基于目前的结果，1,25（OH）2D 通过靶向 c-Myc 和 FOXO1 的表达，在体外对 OS 细胞表现出抗侵袭、抗迁移和抗增殖作用。我们的研究结果表明，有效的 1,25（OH）2D 剂量可能降低 OS 细胞系的侵袭潜能。但是，还需要进一步的研究和临床试验。
