Effect of Inorganic Phosphorus Manipulation on the Growth and Progression of Prostate Cancer Cells in vitro

Epidemiological studies have linked higher serum and dietary phosphorus to an in-creased risk of prostate cancer (PC) and its lethal state. These findings do not distinguish between the impact of inorganic phosphorus (Pi) per se or its homoeostatic regulators. Thus, this study aimed to determine the in vitro tumorigenic effects of elevated Pi concen-trations per se on androgen-dependent epithelial-like PLum-AD murine PC cells at molec-ular 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 poten-tial sodium- dependent Pi uptake mechanism. Furthermore, physiologically relevant ele-vated concentrations of NaPi (3 mM) and KPi (1 and 3 mM) increased relative vimentin expression of PLum-AD PC cells, a biomarker of EMT. Our findings suggest that elevated Pi levels per se, in hyperphosphatemia range, can directly promote EMT in PC, highlight-ing its potential role in tumor progression.