Expression and Significance of SHP-1/p21/CDK6/Cyclin D1 in Nasopharyngeal Carcinoma Cells with Different Radiosensitivity
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摘要: 目的 建立鼻咽癌放射抗拒亚系CNE-2S,研究SHP-1/p21/CDK6/Cyclin D1通路在鼻咽癌细胞系CNE-2和CNE-2S中表达的差异,探讨鼻咽癌放射敏感度变化的分子机制。方法通过X线大剂量低分割照射技术建立鼻咽癌放射抗拒亚系(子代,CNE-2S1),观察亲代(CNE-2)和子代细胞的形态学和生长动力学差异,检测亲代及子代细胞系放射敏感度相关参数,分析亲代及子代细胞系各自细胞周期分布,同时检测亲代与子代细胞系 SHP-1/p21/CDK6/Cyclin D1通路中各因子的蛋白质表达水平。结果通过X线大剂量低分割照射技术成功建立鼻咽癌放射抗拒亚系CNE-2S1,且CNE-2及CNE-2S1放射敏感度相关参数具有延续性。同时CNE-2S1细胞S期比例较CNE-2细胞明显增高,G1期细胞明显减少,G2-M期细胞比例变化不明显。此外SHP-1、CDK6以及CylinD1在CNE-2S1细胞中的蛋白表达水平明显上调,p21表达水平则明显下调,其与CNE-2细胞之间的差异具有统计学意义。结论SHP-1/p21/CDK6/Cyclin D1通路可能在调控鼻咽癌放射敏感度和细胞周期分布方面发挥一定作用。Abstract: Objective To establish radiation-resistant nasopharyngeal carcinoma cell subline CNE-2S and reveal the relationship between expression levels of SHP-1/p21/CDK6/Cyclin D1 and radiation-resistance in nasopharyngeal carcinoma cells. Methods Radiation-resistant nasopharyngeal carcinoma cell subline was set up by X-ray hypofractionted radiotherapy.The differences on morphology and growth kinetics between different passengers were observed.The cell cycles of different passengers were analyzed.The protein levels in SHP-1/p21/CDK6/Cyclin D1 signaling pathway were examined in various clones of cells. Results The X-ray hypofractionted radiotherapy could build radioresistant subline of nasopharyngeal carcinoma.Meanwhile,the percentage of CNE-2S1 cells in S phase was significantly increased than that of CNE-2 cells,G1 phase cells were decreased significantly,G2-M phase cells had no obvious change.In addition,protein levels of SHP-1,CDK6,and CylinD1 in CNE-2S1 cells were significantly increased,but the expression of p21 was significantly reduced than that of CNE-2 cells. Conclusion SHP-1-p21-CyclinD1-CDK6 pathway may have a certain role in radiation sensitivity and cell cycle distribution of nasopharyngeal carcinoma.
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Key words:
- Radiation-resistant /
- Cell cycle /
- SHP-1 /
- Nasopharyngeal carcinoma
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