Polo樣激酶1在非霍奇金淋巴瘤中的表達(dá)及其意義.pdf

1、華中科技大學(xué)博士學(xué)位論文Polo樣激酶1在非霍奇金淋巴瘤中的表達(dá)及其意義姓名：劉林申請(qǐng)學(xué)位級(jí)別：博士專業(yè)：內(nèi)科學(xué)（血液病學(xué)）指導(dǎo)教師：鄒萍20080501華 中 科 技 大 學(xué) 博 士 學(xué) 位 論 文華 中 科 技 大 學(xué) 博 士 學(xué) 位 論 文 IIIAbstract Objective: The study was designed to investigate expression of Polo like kinase 1 (P

2、LK1) 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

3、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

4、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 immunopreci

5、pitation, 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 t

6、reated 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

7、.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-

8、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

9、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