PLK1 downregulation by RO3280 prevents cell proliferation, migration, and invasion via the Wnt/β-catenin pathway in prostate cancer

Abstract

IntroductionHigher expression levels of serine/threonine-protein kinase 1 (PLK1) are significantly associated with tumorigenesis and poor clinical prognoses. Consequently, PLK1 is considered a latent target in cancer treatment. We aimed to determine the cytotoxic effects of RO3280 on prostate cancer cells.Material and methodsPLK1 expression was investigated using real-time PCR and western blotting in prostate cancer tissues and paired normal tissues. Real-time cell analysis, cell counting kit-8 assays, and 5-ethynyl-2¢-deoxyuridine cell proliferation assays were applied for the examination of cell proliferation ability. Wound healing assays and transwell assays were used to assess the migratory and invasive abilities of the prostate cancer cell lines with or without RO3280 treatment. Moreover, the target genes and pathways were detected by transcriptomics RNA sequencing in the cells cultured in RO3280 and through a series of bioinformatics analyses. Finally, the Wnt/β-catenin pathway was screened out and verified by western blotting.ResultsWe observed the mRNA and protein overexpression of PLK1 in the prostate cancer cells and tissues. The inhibition of PLK1 by RO3280 significantly reduced the migratory, invasive, and proliferative properties of the RO3280-treated cancer cell lines compared with their controls. RO3280 mediated the inactivation of the Wnt/β-catenin pathway, and reduced the rates of cell proliferation, migration, and invasion in prostate cancer cells.ConclusionsThis study’s findings are significant owing to the identification of the specific anticancer mechanism of RO3280, which may have therapeutic effects. This trial provides clarity on the feasibility of the use of RO3280 as a cancer therapeutic agent for prostate cancer.