抑制Polo样激酶1对鼻咽癌细胞辐射敏感性的影响

发布时间：2018-06-22 10:00

本文选题：Polo样激酶 + 鼻咽癌　；参考：《中国肿瘤生物治疗杂志》2017年03期

【摘要】：目的:探索抑制Polo样激酶1(Polo-like kinase 1,PLK1)对鼻咽癌(nasopharyngeal carcinoma,NPC)细胞CNE-1和CNE-2辐射敏感性的影响。方法:分别运用siRNA和小分子抑制剂BI2536抑制CNE-1和CNE-2细胞内PLK1的表达或磷酸化,通过MTT法检测抑制PLK1对NPC细胞增殖能力的影响,流式细胞技术检测对细胞周期和凋亡的影响,细胞免疫荧光检测对辐射后DNA损伤位点的影响,克隆形成实验及曲线拟合计算对辐射后细胞放射生物参数和放射增敏比(sensitization enhancement ratio,SER)的影响。结果:与对照组相比,抑制PLK1可以明显抑制NPC细胞增殖,并诱导细胞发生G2-M期阻滞和有丝分裂灾难。抑制NPC细胞PLK1联合射线辐射后,NPC细胞克隆形成能力下降(CNE-1:P0.05;CNE-2:P0.05),且随着BI2536浓度的增大克隆形成能力下降更加明显(CNE-1:P0.05;CNE-2:P0.05);细胞生存分数明显降低(均P0.05);核中γ-H2AX位点数目明显增加(P0.05);细胞凋亡率显著升高(均P0.05);siR-PLK1转染CNE-1和CNE-2后SER分别为1.1988和1.3198,BI2536处理CNE-1和CNE-2后SER分别为1.5508和1.2028。结论:抑制PLK1可以抑制NPC细胞增殖,诱导发生细胞周期阻滞和有丝分裂灾难,并能显著提高NPC细胞辐射敏感性。
[Abstract]:Objective: to investigate the effects of inhibition of Polo-like kinase 1 (PLK1) on the radiosensitivity of nasopharyngeal carcinoma-NPC cells CNE-1 and CNE-2. Methods: siRNA and small molecule inhibitor BI2536 were used to inhibit the expression or phosphorylation of PLK1 in CNE-1 and CNE-2 cells, MTT assay was used to detect the effect of inhibiting PLK1 on the proliferation of NPC cells, and flow cytometry was used to detect the effects on cell cycle and apoptosis. The effects of cellular immunofluorescence assay on DNA damage sites after irradiation and the effects of clone formation and curve fitting on radio-biological parameters and radiosensitization ratio (sensitization enhancement ratiosier) of irradiated cells were studied. Results: compared with the control group, the inhibition of PLK1 significantly inhibited the proliferation of NPC cells and induced G2-M phase arrest and mitotic disaster. The clone forming ability of NPC cells decreased after the inhibition of PLK1 combined with radiation (CNE-1: P0.05, CNE-2: P0.05), and decreased more obviously with the increase of BI2536 concentration (CNE-1: P0.05, CNE-2: 2: P0.05), the survival fraction of cells decreased significantly (P0.05), and the number of 纬 -H2AX loci in the nucleus increased significantly (P 0.05), and the number of 纬 -H2AX sites in the nucleus increased significantly with the increase of the concentration of BI2536 (CNE-1: P 0.05). After transfection of CNE-1 and CNE-2, the SER of CNE-1 and CNE-2 were 1.1988 and 1.3198 BI2536, respectively. The SER of CNE-1 and CNE-2 treated with BI2536 was 1.5508 and 1.2028 respectively. Conclusion: inhibition of PLK1 can inhibit the proliferation of NPC cells, induce cell cycle arrest and mitotic disaster, and can significantly increase the radiosensitivity of NPC cells.
【作者单位】：南方医科大学第一临床医学院;深圳市人民医院放疗科;南方医科大学南方医院放疗科;
【基金】：国家自然科学基金资助项目(No.81572964,No.81274508) 广东省自然科学基金资助项目(No.2014A030313289) 广东省教育厅科研资助项目(No.2013KJCX0038)~~
【分类号】：R739.63

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