Testicular nuclear receptor 4 affects the chemo sensitivity of prostate cancer DU145 cells to docetaxel by regulating microRNA-145 expression

Abstract

Objective To investigate whether testicular nuclear receptor 4 (TR4) affects the chemo-sensitivity of prostate cancer DU145 cells to docetaxel by regulating microRNA-145 (miR-145) expression. Methods The expression of TR4 was overexpressed or inhibited in prostate cancer DU145 cells, the microRNA-145 (miR-145) status in those cells was evaluated. Luciferase assay was used to detect whether TR4 could affect the activity of miR-145 promoter. Different concentration of docetaxel were added to those DU145 cells which were either inhibited the expression of TR4, miR-145 or both, 48 hours later, cell counting kit-8 (CCK-8) assay was used to detect the cell activity in each group, and the half maximal inhibitory concentration (IC50) were calculated. Results MiR-145 significantly decreased when TR4 is overexpressed and vice versa; The activity of miR-145 promoter was significantly increased when TR4 was suppressed (P=0.016); when TR4 was inhibited, the chemo sensitivity of DU145 to docetaxel were increased with a lower IC50 value (2.602 μg/ml) as compared to that of control group (5.397 μg/ml) (P=0.001). When miR-145 was suppressed, the chemo-sensitivity of DU145 cells to docetaxel were decreased with a higher IC50 value (6.179 μg/ml) as compared to control group (3.549 μg/ml) (P=0.001). When both TR4 and miR-145 were inhibited in DU145 cells, they had a similar IC50 (4.578 μg/ml) as compared to that of the control group (4.122 μg/ml) (P=0.123). Conclusion TR4 could influence the chemo sensitivity of prostate cancer DU145 cells to docetaxe by transcriptionally regulating the expression of miR-145. Key words: Prostate cancer; Testicular nuclear receptor 4; MicroRNA-145; Docetaxel; Half maximal inhibitory concentration