【作者】 范凯；

【导师】 吕申；

【作者基本信息】 大连医科大学 ， 病理学与病理生理学， 2006， 博士

【摘要】 目前,针对肿瘤的治疗有手术、化疗、放疗和基因治疗等多种治疗手段。对于大多数肿瘤,常常需要两种以上手段联合治疗。临床实践发现,某些肿瘤(如肺癌、鼻咽癌、宫颈癌等)在接受放疗后会产生对化疗药物的多药耐药,但迄今为止对这方面的研究报道不多见。现已明确,肿瘤接受化疗后会出现肿瘤细胞的多药耐药,这种耐药性的产生涉及耐药基因、DNA修复基因等多种基因。由于放疗和多数化疗药物的作用靶点均为DNA,而且,在两种情况下,受损伤的DNA都需经过细胞修复系统的修复。由此推测,肿瘤细胞在放疗后产生的多药耐药性是否也与耐药蛋白和DNA修复系统有关呢?另外,研究发现,DNA修复系统的功能不仅是决定肿瘤细胞对化疗药物敏感性的重要因素,而且也直接影响到肿瘤细胞的放射敏感性。针对上述问题,本研究从以下几个方面进行研究。目的:研究肿瘤细胞接受射线照射后耐药相关基因和DNA修复基因的表达,探讨放疗后肿瘤细胞产生多药耐药的机制,为临床合理安排肿瘤放化疗顺序、避免因放疗诱导的多药耐药,提高肿瘤综合治疗效果提供理论依据。方法:选取人系鼻咽癌CNE细胞株,利用X射线作为照射源对该细胞株进行照射。细胞每次接受照射的剂量为2Gy,1次/天,连续照射5天,照射总剂量为10Gy。每次照射后将细胞放回CO2孵箱内继续培养,照射全部结束后立即收集部分细胞,其余细胞继续培养,待细胞进入对数生长期后每周收集1次,共收集5次(即照射终止后即刻,1-4W),冻存备用。光镜和透射电镜下观察照射前后细胞形态;采用MTT法检测照射后细胞对化疗药物顺铂(cDDP)、5-氟尿嘧啶(5-FU)更多还原

【Abstract】 So far, surgical, drug, radiation and biological treatments have been adopted for tumor therapy. Generally, more than two ways are necessary to most cancer. In recent years, it has been found that resistance to drug after radiation for some tumors (nasopharyngeal carcinoma, lung cancer) emerges, which is the major impediment to successful treatment of many tumor typesAt present, it has been clarified that multidrug resistance of tumor occurs after chemotherapy, which involves many genes such as drug resistance genes, DNA repair gene. Because the targets of radiotherapy and chemotherapy are both DNA, moreover, lesioned DNA both need repair, it is supposed that multi-drug resistance of tumor after radiation is probably related to drug resistance genes and DNA repair system. In addition, it has been found that DNA repair system is not only associated with cellular sensitivity to chemotherapy, but also with cellular sensitivity to radiotherapy. This study was performed on basis of following considerations.Objective: To explore mechanisms of multi-drug resistance and DNA repair of tumor after radiation by studying the expression of drug resistance genes and DNA repair genes in nasopharyngeal carcinoma CNE cells after X-radiation and to establish theoretical basis for improvement effect of chemotherapy and radiotherapy of tumor.Methods: The CNE cells were exposed to 5 fractions of 10 Gy of X-radiation, once exposure daily. After the final exposure, the partial cells were harvested and the rest were allowed to repopulate in culture medium. Cells were harvested once a week and 5 times totally(0-4th weeks after更多还原