Targeting Polo Like Kinase 1 As A Novel Therapeutic Approach For Non-Hodgkin's Lymphoma

Objective: The study was designed to investigate expression of Polo like kinase 1 (PLK1) in non-Hodgkin's lymphoma (NHL) and target it as a novel therapeutic approach for non-Hodgkin's lymphoma.Methods: The expression of PLK1 and survivin were detected with immunohistochemical techniques, and assessed their significance in predicting prognosis. Jurkat and Raji cells were irradiated by Co-60(10Gy) or treated by adriamycin (ADM, 0.5μM); After treatment, cell cycle distribution was detected by fluorescein activated cell sorter (FACS), nuclear phospho-γ-Histone H2AX staining was detected by laser scanning confocal microscope (LSCM), PLK1 protein expression and kinase activity assay was tested by western blotting (WB) and immunoprecipitation, respectively. SiRNA plasmid to specifically depleting PLK1 gene was transfected into Jurkat and Raji cells, PLK1 mRNA and protein expression was detected by RT-PCR and WB; transfected cells were irradiated or treated by ADM; cell cycle distribution was detected by FACS, nuclear phospho-γ-Histone H2AX staining was detected by LSCM; apoptosis was assayed by AnnexinⅤ/ APC.Results: The expression rate of PLK1 and survivin were 63.6 % (56/88) and 79.5% (70/88) in NHL, respectively. PLK1 expression correlated with systemic symptom, LDH level and IPI scores in B-NHL and T-NHL, while survivin did not. PLK1 expression correlated with shortened event-free survival (EFS) using the Log-rank test in B-NHL and T-NHL, but survivin did not. Cox regression analysis identified the independent prognostic significance for PLK1.After DNA damage treatment, Jurkat and Raji cells were arrested at cell cycle G2/M, nuclearγ-Histone H2AX staining was positive, PLK1 kinase activity was inhibited, but protein expression was not affected; After repair, cells recovered from DNA damage, and entered into next cell cycle. SiRNA-PLK1 could greatly reduce PLK1 mRNA and protein expression, hamper the cell cycle progress of cells recovered from DNA damage, and induce apoptosis. Conclusion: PLK1 was overexpressed in NHL and could be treated as an independent prognostic factor. PLK1 gene silence combined with traditional chemotherapy or irradiation could hamper the cell cycle progress and induce apoptosis.