Polo-like kinase 1 contributes to the tumorigenicity of BEL-7402 hepatoma cells via regulation of Survivin expression.

摘要

Polo-like kinase 1 (PLK1) is required for multiple stages of mitosis and has been found to be overexpressed in many human malignancies. Previous studies by our group have revealed PLK1 overexpression as an independent prognostic factor for hepatocellular carcinoma (HCC). However, the underlying mechanisms of the tumorigenetic effects of PLK1 in HCC remain unclear. In this study, we depleted PLK1 in human hepatoma BEL-7402 cells using small interfering RNA. Flow cytometry analysis showed that PLK1 depletion resulted in a threefold increase in the G2/M population, with a resultant decrease in the G(1) population. Importantly, PLK1 depletion reduced the tumorigenicity of BEL-7402 cells in vivo, evidenced by significantly slower tumor growth following subcutaneous innoculation of tumor cells in the flanks of BALB/c nude mice. Furthermore, more apoptotic bodies associated with decreased Survivin protein expression and increased level of active caspase-3 were observed in tumor tissues of the PLK1 depletion group by TUNEL assay, Western blot and immunohistochemical analysis, respectively. Collectively, our findings imply that PLK1 depletion led to G2/M arrest, inhibition of cell proliferation and promotion of apoptosis via downregulation of Survivin expression, suggesting that PLK1 represents a new therapeutic target for HCC.