Hypoxia-inducible factor 1α (HIF-1α) mediates the epithelial-mesenchymal transition in benign prostatic hyperplasia

Abstract

Background: Epithelial-mesenchymal transition (EMT) based cancer cell invasion and metastasis has been thoroughly studied in prostate cancer. It was well known that EMT markers which have been found in benign prostatic hyperplasia (BPH) tissues, but system descriptions have not been described. Methods: First, in order to construct the epithelial cells to mesenchymal cell transformation model, BPH-1 cells were cultured with supernatant of prostate matrix normal prostate stromal WPMY-1 cells, after obtaining the culture medium through a filter. After that, we observed the morphology of cells cultured for a period of time by microscopy, detected cell invasion ability by transwell assay, detected cell proliferation ability by MTT, and detected EMT marker expression by western. Finally, we treated the cells with anti-HIF-1α drugs to study their effects on EMT, and then tested several related proteins simultaneously. Results: The results showed that the morphology of BPH-1 cells gradually changed to fusiform after cultured with WSCM. At the same time, E-cadherin and cytokeratin levels were significantly lower than those in normal medium. Simultaneous detection of vimentin (SMA) and Snail was positive compared to normal cultured cells. At the same time, the cells were cultured with WSCM and the invasive ability was up-regulated. After treatment with anti-HIF-1α drug, E-cadherin and CK5/8 protein expression was up-regulated, but vimentin, α-SMA, and Snail expression was down-regulated, and in addition, p-Smad3 protein expression was also down-regulated after anti-HIF-1α drug was added. Conclusion: The above results indicated that WSCM-1 stromal cell supernatant WSCM can induced BPH-1 cell interstitialization, and at the same time, by inducing EMT, secreting HIF-1α activates Smad3 signaling. Our study shows that inhibition of HIF-1α expression provides a new reference for clinical treatment of BPH.