中国肿瘤生物治疗杂志2017，Vol.24Issue(3)：222-229,8.DOI:10.3872/j.issn.1007-385X.2017.03.002
抑制Polo样激酶1对鼻咽癌细胞辐射敏感性的影响
Effect of inhibiting Polo-like kinase 1 on radiosensitivity of nasopharyngeal carcinoma cells
摘要
Abstract
Objective:To explore effect of inhibiting Polo-like kinase 1 (PLK1) on radiosensitivity of nasopharyngeal carcinoma (NPC) CNE-1 and CNE-2 cell lines.Methods:Using small interfering RNA (siRNA) and small molecule inhibitor BI2536 to inhibit expression and phosphorylation of PLK1 in the CNE-1 and CNE-2 cells respectively.Effect of inhibiting PLK1 on proliferation ability of the NPC cells was tested by MTT assay.Flow cytometry assay was used to detect effect of the inhibition on cell cycle and apoptosis of the NPC cells and immuno fluorescence assay was used to assess the effect of damage sites of DNA in the NPC cells after radiation.Clone formation experiment and curve fitting assay were used to calculate radiation parameters and sensitization enhancement radio (SER) of the NPC cells after radiation.Results:Compared with the control group,inhibition of PLK1 in the NPC cells reduced proliferation of the NPC cells and,induced G2-M arrest and mitotic catastrophe of the NPC cells.Inhibition of PLK1 in the NPC cells combined with irradiation significantly decreased ability of cell colony formation in the NPC cells (CNE-1:P ＜ 0.05,CNE-2:P ＜ 0.05),and with increasing concentration of the B12536,the ability of cell colony formation in the NPC more pronounced declined (CNE-1:P ＜ 0.05,CNE-2:P ＜ 0.05).In addition,Inhibition of PLK1 in the NPC cells combined with irradiation reduced the cell survival fraction,increased the number of γ-H2AX loci in nucleus of the cells,and accelerated apoptosis rate of the cells obviously (all P ＜0.05).SER of the CNE-1 and the CEN2 cells were 1.1988 and 1.3198 respectively after transfection of them with siR-PLK1.And SER of the CNE-1 and the CEN-2 cells were 1.5508 and 1.2028 respectively after treatment of them with the B12536.After treatment of the CEN-1 and the CEN-2 cells with the B12536.Conclusion:Inhibition of PLK1 could suppress infiltration of the NPC cells,induce cell-cycle arrest and mitotic catastrophe,and significantly enhance radiosensitivity of the NPC cells.关键词
Polo样激酶1/鼻咽癌/小分子抑制剂BI2536/辐射敏感性Key words
Polo-like kinase 1 (PLK1)/nasopharyngeal carcinoma (NPC)/small molecule inhibitor BI2536/radiosensitivity分类
医药卫生引用本文复制引用
杨红丽,王栢耀,袁亚维..抑制Polo样激酶1对鼻咽癌细胞辐射敏感性的影响[J].中国肿瘤生物治疗杂志,2017,24(3):222-229,8.基金项目
国家自然科学基金资助项目(No.81572964,No.81274508) （No.81572964,No.81274508）
广东省自然科学基金资助项目(No.2014A030313289) （No.2014A030313289）
广东省教育厅科研资助项目(No.2013KJCX0038).Project supported by the National Natural Science Foundation of China(No.81572964,No.81274508),the Natural Science Foundation of Guangdong Province(No.2014A030313289),and the Science Reasearch Project from Educational Commission of Guangdong Province(No.2013KJCX0038) （No.2013KJCX0038）
