Kourie Christina Mary, Ghamlouche Fatima, Hachem Sana, Yehya Amani, Jaafar Layal, El-Mallah Carla, Abou-Kheir Wassim, Obeid Omar
Department of Nutrition and Food Science, Faculty of Agriculture and Food Sciences, American University of Beirut, Beirut P.O. Box 11-0236, Lebanon.
Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut P.O. Box 11-0236, Lebanon.
Int J Mol Sci. 2025 May 16;26(10):4762. doi: 10.3390/ijms26104762.
Epidemiological studies have linked higher serum and dietary phosphorus to an increased risk of prostate cancer (PC) and its lethal state. However, these findings do not distinguish between the impact of inorganic phosphorus (Pi) and the impacts of its homoeostatic regulators. Thus, this study aimed to determine the in vitro tumorigenic effects of elevated Pi concentrations on androgen-dependent epithelial-like PLum-AD murine PC cells at molecular and cellular levels. Physiologically attainable elevated levels and supraphysiological levels of sodium (NaPi) and potassium phosphate (KPi) were used to assess PLum-AD cell proliferation, viability, migration, and epithelial-mesenchymal transition (EMT) marker expression, which were determined by the thiazolyl blue tetrazolium bromide cell assay, trypan blue exclusion assay, wound healing assay, and immunofluorescence staining, respectively. Treatment of Plum-AD cells with supraphysiological levels of NaPi (20 mM) significantly reduced cell proliferation, whereas KPi did not, suggesting a potential sodium-dependent Pi uptake mechanism. Furthermore, physiologically relevant elevated concentrations of NaPi (3 mM) and KPi (1 and 3 mM) increased the relative vimentin expression of PLum-AD PC cells, a biomarker of EMT. Our findings suggest that elevated Pi levels , in the hyperphosphatemia range, can directly promote EMT in PC, highlighting the potential role of Pi in tumor progression.
流行病学研究已将较高的血清磷和膳食磷与前列腺癌（PC）及其致死状态的风险增加联系起来。然而，这些发现并未区分无机磷（Pi）的影响及其稳态调节因子的影响。因此，本研究旨在在分子和细胞水平上确定升高的Pi浓度对雄激素依赖性上皮样PLum-AD小鼠PC细胞的体外致瘤作用。使用生理上可达到的升高水平以及超生理水平的磷酸钠（NaPi）和磷酸钾（KPi）来评估PLum-AD细胞的增殖、活力、迁移和上皮-间质转化（EMT）标志物表达，分别通过噻唑蓝四唑溴盐细胞测定、台盼蓝排斥测定、伤口愈合测定和免疫荧光染色来确定。用超生理水平的NaPi（20 mM）处理Plum-AD细胞可显著降低细胞增殖，而KPi则不会，这表明存在潜在的钠依赖性Pi摄取机制。此外，生理相关的升高浓度的NaPi（3 mM）和KPi（1和3 mM）增加了PLum-AD PC细胞的波形蛋白相对表达，波形蛋白是EMT的生物标志物。我们的研究结果表明，高磷血症范围内升高的Pi水平可直接促进PC中的EMT，突出了Pi在肿瘤进展中的潜在作用。
