10Gy X线照射鼻咽癌移植瘤组织差异蛋白质的初步筛选

发布时间：2018-03-22 14:10

本文选题：鼻咽癌　切入点：移植瘤　出处：《广西医科大学》2014年硕士论文　论文类型：学位论文

【摘要】：目的鼻咽癌(nasopharyngeal carcinoma，NPC)是一种常见于我国华南地区的恶性肿瘤，以放疗为主要治疗方式。临床上少部分病人治疗后出现局部残留、复发或远处转移，其中，癌细胞对放射抗拒可能是局部残留和复发的重要因素。因此探寻放射抗拒机制将为鼻咽癌临床放疗增敏提供理论指导。本研究将鼻咽癌细胞株移植裸鼠体内成瘤旨在模拟体内环境下考察鼻咽低分化鳞癌CNE-2细胞与其放射抗拒细胞株CNE-2R移植瘤组织在接受大剂量射线后蛋白质表达变化，考量两者对射线的耐受性，以期探寻与鼻咽癌放射抗拒相关机制。为临床鼻咽癌放射治疗中预测放疗敏感性的个体差异，进一步探寻放射敏感性分子标记物提供实验基础。方法1、建立鼻咽癌细胞株裸鼠移植瘤模型并提取瘤体组织蛋白。2、提取瘤体组织总蛋白质并酶解成肽段，运用iTRAQ标记技术与二维液相色谱联用LTQ-Orbitrap质谱分离技术，在LTQ-Orbitrap高分辨率质谱仪上鉴定并筛选差异表达蛋白质。3、对鉴定的差异表达蛋白质进行Gene Ontology生物功能分类。结果通过质谱鉴定分析10GyX线照射后鼻咽癌移植瘤组织蛋白质共2762种。鼻咽癌低分化鳞癌CNE-2细胞及其放射抗拒细胞株CNE 2R移植瘤组织差异表达蛋白质61个，，其中上调17个，下调44个。分析显示差异蛋白质主要涉及细胞周期调控、分解代谢、信号通路调节、压力应激反应及氧化还原反应等生物过程。差异较大的Annexin2、PDIA3、Ubiquitin、CKAP4、HSPA8、14-3-3δ/ζ、NLRC4参与这些生物过程中。结论 Annexin2、PDIA3、Ubiquitin、CKAP4、HSPA8、14-3-3δ/ζ、NLRC4差异表达蛋白质可能与鼻咽癌放射抗拒相关。
[Abstract]:Purpose. Nasopharyngeal carcinoma (NPC) is a common malignant tumor in southern China. Radiotherapy is the main method of treatment. Cancer cell resistance to radiation may be an important factor in local residual and recurrence. Therefore, exploring the mechanism of radiation resistance will provide theoretical guidance for the clinical radiosensitization of nasopharyngeal carcinoma. The aim of this study was to investigate the changes of protein expression in nasopharyngeal poorly differentiated squamous cell carcinoma (CNE-2) cell line and its radioresistant cell line (CNE-2R) transplanted tumor in nude mice. In order to explore the mechanism of radioresistance in nasopharyngeal carcinoma (NPC), we can provide the experimental basis for predicting the radiosensitivity of nasopharyngeal carcinoma (NPC) and further exploring the molecular markers of radiosensitivity. Methods 1. The tumor transplantation model of nasopharyngeal carcinoma (NPC) cell line in nude mice was established and the tumor tissue protein was extracted. The total protein of the tumor tissue was extracted and enzymatically hydrolyzed into peptide segment. LTQ-Orbitrap mass spectrometry was used to separate the tumor tissue with iTRAQ labeling technique and two-dimensional liquid chromatography-mass spectrometry (LC-MS). The differentially expressed protein. 3 was identified and screened by LTQ-Orbitrap high resolution mass spectrometer. The differential expressed protein was classified by Gene Ontology biological function. Results. There were 2762 kinds of proteins in the transplanted tumor tissues of nasopharyngeal carcinoma (NPC) irradiated by 10GyX line by mass spectrometry. There were 61 differentially expressed proteins in CNE-2 cells of poorly differentiated nasopharyngeal carcinoma and their radioresistant cell lines, 17 of which were up-regulated. The differential proteins were mainly involved in biological processes such as cell cycle regulation, catabolism, signal pathway regulation, pressure stress response and redox reaction. The relatively different Annexin 2, PDIA3, PDIA3, CKAP4 and HSPA83-3 未 / 味 NLRC4 were involved in these biological processes. Conclusion. The differentially expressed proteins of Annexin 2, PDIA3, UbiquitininCK-AP4, HSPA814-3-3 未 / 味 NLRC4 may be related to the radioresistance of nasopharyngeal carcinoma.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R739.63

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