Background: Silybin was known to exert inhibition in prostate cancer, but the underlying mechanism remained largely unknown. This study was designed to find out the potential target of Silybin on prostate cancer and explore the relative mechanisms.
Methods: Firstly, we screened the possible targets of Silybin through the PubChem database and Subpathway - GM. Then DU145 cells were transferred to investigate the correction about related targets, magnetic bead sorting and flow cytometry were used to sort and identify the cells. Proliferation, migration and invasion ability of DU145 cells were detected by MTT assay, Transwell assay, plate clonality and sphere formation assay. BALB/c nude mice were constructed models with implanted sarcoma and measured the tumor volume every 5 days as wells tumor weight. The levels of proteins were detected by Western blot and immunocytochemistry. RT-PCR was selected to test the expression of protein's mRNA.
Results: It was screened out the ALDH1A1 was highly correlated with subpathways of the Silybin risk metabolic pathway. And ALDH1A1 expression was positively correlated RARα with Ets1 by interfering with the ALDH1A1 gene. Importantly, ALDH1A1(+) cells showed proliferation, migration and invasion ability. In addition, it showed that Silybin exerted the inhibition on prostate cells by suppressed the proliferation, migration and invasion ability of cells in vitro experiment. Silybin also reduced the tumor volume and weight. And Silybin displayed obviously reduced the proteins and mRNA of ALDH1A1, RARα, Ets1 and MMP9 expressions.
Conclusion: Our results indicated that Silybin showed inhibition of prostate cancer and the mechanism was involving with downregulating ALDH1A1 expression, thereby inhibiting the activation of RARα and preventing the activation of Ets1 to inhibit the growth and invasion of prostate cancer.
Keywords: ALDH1A1; biomarker; metabolism pathway; prostate cancer; silybin.
Copyright © 2020 Jiang, Song, Jiang, Qiao, Yang, Wang and Li.