Effect of LSD1 inhibitors on regulating the biological behaviors of prostate cancer cells in vitro

Abstract

Objective To investigate the effect of lysine-specific demethylase-1 (LSD1) inhibitor Eutonyl on the proliferation, migration and epithelial-mesenchymal transition and other in vitro biological behaviors of androgen-independent human prostate cancer cells. Methods Tumor cells were treated with different concentrations of Eutonyl (0, 1, 3 mmol/L) for 0-72 h. The cell viability was measured by CCK8 assay. After treatment with 0 and 3 mmol/L Eutonyl for 48 h, the cell apoptosis and the distribution of cell cycle were compared by flow cytometry, and the cell viability was detected by the scratch test and Transwell chamber test. Western-blot was adopted to measure the protein expression of key genes in the process of epithelial mesenchymal transition. RT-qPCR was performed to further verify the changes in mRNA levels to elucidate the effect of LSD1 inhibitor Eutonyl on prostate cancer cells. Results Eutonyl at a dose of 1 and 3 mmol/L could significantly reduce the survival rate and colony formation of DU145 cells. The most significant effect was obtained after 3 mmol/L Eutonyl treatment for 48 h. Eutonyl treatment at a dose of 3 mmol/L for 48 h could significantly increase the apoptosis rate of prostate cancer cells and evidently increased the quantity of cells in the G2 phase. The healing rate of scratch test was significantly slowed and the quantity of cells passing through the chamber was significantly reduced in the treatment groups. The results at the protein and mRNA levels were consistent, suggesting that the process of epithelial-mesenchymal transition was significantly inhibited. Conclusion LSD1 inhibitor can significantly inhibit the proliferation of prostate cancer cells by promoting cell apoptosis and arresting cell cycle, weakening the migration ability of tumor cells, and significantly suppress the epithelial-mesenchymal transition process. LSD1 may be a potential therapeutic target for clinical treatment of prostate cancer. Key words: Prostate neoplasm; LSD1 inhibitor; Eutonyl; Cytology