通过向肝素结合蛋白17/纤维细胞生长因子结合蛋白1与维生素D3或eledecalcitol治疗状细胞癌的潜在治疗方法
Tomoaki Shintani1, Mirai Higaki2, Siti Nur Zawani Rosli2,3
1Center of Oral Clinical Examination, Hiroshima University Hospital, Hiroshima, 734-8551, Japan. tshintan@hiroshima-u.ac.jp.
概括
纤维细胞生长因子结合蛋白1 (FGFBP-1) 促进状细胞癌 (SCC) 的生长. 用维生素D类型的FGFBP-1抑制,如利醇,为SCC提供了潜在的向治疗.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 肝素结合蛋白17 (HBp17),现在被称为纤维细胞生长因子结合蛋白1 (FGFBP-1),是由上皮细胞分泌的.
- FGFBP-1与多个纤维细胞生长因子 (FGFs) 结合,这表明在它们的运输和功能中发挥了作用.
- 以前的研究已经探索了FGFBP-1在状细胞癌 (SCC) 的功能及其作为治疗点的潜力.
研究的目的:
- 研究FGFBP-1在SCC细胞增殖和瘤性中的作用.
- 探索在SCC中准FGFBP-1的治疗潜力.
- 评价1α,25(OH) 2D3或其类型的甲酸 (ED-71) 在抑制FGFBP-1表达和瘤生长方面的疗效.
主要方法:
- 在A431-4细胞中FGFBP-1的转基因表达,以评估增殖和瘤性.
- 基因组编辑以创建FGFBP-1淘汰赛 (KO) 细胞并评估瘤生长,运动和分化标志物.
- 用1α,25(OH) 2D3或ED-71进行治疗,以分析对FGFBP-1表达,瘤生长和NF-κB信号通路的影响.
主要成果:
- 在体外,FGFBP-1表达增强了SCC细胞的增殖,并在体内产生瘤性.
- FGFBP-1淘汰赛显著抑制了瘤生长,细胞运动性和瘤性,并增加了促进分化分子的表达.
- 1α,25(OH) 2D3和ED-71通过抑制NF-κB信号通路来抑制FGFBP-1表达和瘤生长.
结论:
- FGFBP-1在促进SCC扩散和瘤性方面发挥着至关重要的作用.
- 用1α,25(OH) 2D3或ED-71针对FGFBP-1的向显示了SCC的显著治疗潜力.
- 这些发现支持开发FGFBP-1向分子疗法,特别是口服SCC.
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