Inhibition of the proliferation, invasion, migration, and epithelial-mesenchymal transition of prostate cancer cells through the action of on the TGF-β/Smad pathway.

Background: Prostate cancer (PC) is one of the major male malignancies worldwide. Because Na-K-ATPase is widely involved in various pathological processes, but the action of its α2 subtype () in PC is unclear, we investigated the role of in the invasion and migration of PC cells.

Methods: We measured the expression levels of in human normal prostate epithelial cell line (RWPE-1) and PC cell lines (PC-3 and DU145) by quantitative real-time PCR (qRT-PCR) and western blot. Cell proliferation, apoptosis, migration, and invasion of PC-3 and DU145 cells were investigated through clone formation assay, EdU assay, flow cytometry and transwell assay, respectively. The effect of on a tumor-inhibitory pathway [transforming growth factor-β (TGF-β)/Smad] was assessed using western blot. In addition, tumor formation was detected using xenograft model in male BALB/c nude mice.

Results: The Cancer Genome Atlas (TCGA) analysis showed that expression was reduced in PC patients (P<0.05), and patients with low expression had a lower survival rate (P<0.05). levels were significantly reduced in PC-3 and DU145 cells, compared with RWPE-1 cells (P<0.01). We also demonstrated that overexpression of significantly inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of PC-3 and DU145 cells (P<0.01) and promoted apoptosis (P<0.01). However, silencing had the opposite effect (P<0.01). In addition, overexpression of significantly inhibited the TGF-β/Smad pathway (P<0.01), whereas silencing activated the TGF-β/Smad pathway (P<0.01). Meanwhile, the effect of silencing on the proliferation, apoptosis, migration and invasion was reversed by TGF-β/Smad pathway inhibitor (LY364947). Furthermore, inhibited tumor growth

Conclusions: inhibited proliferation, apoptosis, migration, invasion, and EMT in PC by inhibiting the TGF-β/Smad pathway.