Department of Physiology, University of Hohenheim, 70599 Stuttgart, Germany.
Department of Hematology and Oncology, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany.
Cells. 2021 Dec 23;11(1):40. doi: 10.3390/cells11010040.
Fibroblast growth factor 23 (FGF23) controls vitamin D and phosphate homeostasis in the kidney and has additional paracrine effects elsewhere. As a biomarker, its plasma concentration is associated with progression of inflammatory, renal, and cardiovascular diseases. Major stimuli of FGF23 synthesis include active vitamin D and inflammation. Antineoplastic chemotherapy treats cancer by inducing cellular damage ultimately favoring cell death (apoptosis and necrosis) and causing inflammation. Our study explored whether chemotherapeutics and other apoptosis inducers impact on expression. Experiments were performed in osteoblast-like UMR106 cells, gene expression and protein synthesis were determined by qRT-PCR and ELISA, respectively. Viability was assessed by MTT assay and NFκB activity by Western Blotting. Antineoplastic drugs cisplatin and doxorubicin as well as apoptosis inducers procaspase-activating compound 1 (PAC-1), a caspase 3 activator, and serum depletion up-regulated transcripts while reducing cell proliferation and viability. The effect of cisplatin on transcription was paralleled by up-regulation and NFκB activation and attenuated by Il-6 and NFκB signaling inhibitors. To conclude, cell viability-decreasing chemotherapeutics as well as apoptosis stimulants PAC-1 and serum depletion up-regulate gene expression. At least in part, Il-6 and NFκB may contribute to this effect.
成纤维细胞生长因子 23（FGF23）在肾脏中控制维生素 D 和磷酸盐的稳态，并且具有其他旁分泌作用。作为一种生物标志物，其血浆浓度与炎症、肾脏和心血管疾病的进展相关。FGF23 合成的主要刺激因素包括活性维生素 D 和炎症。抗肿瘤化疗通过诱导细胞损伤来治疗癌症，最终有利于细胞死亡（凋亡和坏死）并引起炎症。我们的研究探讨了化疗药物和其他凋亡诱导剂是否会影响 FGF23 的表达。实验在成骨样 UMR106 细胞中进行，通过 qRT-PCR 和 ELISA 分别测定基因表达和蛋白合成。通过 MTT 测定法评估细胞活力，通过 Western Blotting 测定 NFκB 活性。抗肿瘤药物顺铂和多柔比星以及凋亡诱导剂半胱天冬酶激活化合物 1（PAC-1）、半胱天冬酶 3 激活剂和血清耗竭均上调 转录本，同时降低细胞增殖和活力。顺铂对 转录的影响与 NFκB 激活和 Il-6 和 NFκB 信号转导抑制剂的衰减相平行。总之，降低细胞活力的化疗药物以及凋亡刺激物 PAC-1 和血清耗竭均可上调 基因表达。至少部分原因可能是 Il-6 和 NFκB 参与了这种作用。
