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  本文選題：鼻咽癌　切入點：移植瘤　出處：《廣西醫(yī)科大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：目的 鼻咽癌(nasopharyngeal carcinoma，NPC)是一種常見于我國華南地區(qū)的惡性腫瘤，以放療為主要治療方式。臨床上少部分病人治療后出現(xiàn)局部殘留、復(fù)發(fā)或遠處轉(zhuǎn)移，其中，癌細胞對放射抗拒可能是局部殘留和復(fù)發(fā)的重要因素。因此探尋放射抗拒機制將為鼻咽癌臨床放療增敏提供理論指導(dǎo)。 本研究將鼻咽癌細胞株移植裸鼠體內(nèi)成瘤旨在模擬體內(nèi)環(huán)境下考察鼻咽低分化鱗癌CNE-2細胞與其放射抗拒細胞株CNE-2R移植瘤組織在接受大劑量射線后蛋白質(zhì)表達變化，考量兩者對射線的耐受性，以期探尋與鼻咽癌放射抗拒相關(guān)機制。為臨床鼻咽癌放射治療中預(yù)測放療敏感性的個體差異，進一步探尋放射敏感性分子標記物提供實驗基礎(chǔ)。 方法1、建立鼻咽癌細胞株裸鼠移植瘤模型并提取瘤體組織蛋白。2、提取瘤體組織總蛋白質(zhì)并酶解成肽段，運用iTRAQ標記技術(shù)與二維液相色譜聯(lián)用LTQ-Orbitrap質(zhì)譜分離技術(shù)，在LTQ-Orbitrap高分辨率質(zhì)譜儀上鑒定并篩選差異表達蛋白質(zhì)。3、對鑒定的差異表達蛋白質(zhì)進行Gene Ontology生物功能分類。 結(jié)果 通過質(zhì)譜鑒定分析10GyX線照射后鼻咽癌移植瘤組織蛋白質(zhì)共2762種。鼻咽癌低分化鱗癌CNE-2細胞及其放射抗拒細胞株CNE 2R移植瘤組織差異表達蛋白質(zhì)61個，，其中上調(diào)17個，下調(diào)44個。分析顯示差異蛋白質(zhì)主要涉及細胞周期調(diào)控、分解代謝、信號通路調(diào)節(jié)、壓力應(yīng)激反應(yīng)及氧化還原反應(yīng)等生物過程。差異較大的Annexin2、PDIA3、Ubiquitin、CKAP4、HSPA8、14-3-3δ/ζ、NLRC4參與這些生物過程中。 結(jié)論 Annexin2、PDIA3、Ubiquitin、CKAP4、HSPA8、14-3-3δ/ζ、NLRC4差異表達蛋白質(zhì)可能與鼻咽癌放射抗拒相關(guān)。
[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.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R739.63

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