人鼻咽癌紫杉醇耐药细胞系与其亲代细胞系比较基因组杂交研究

人鼻咽癌紫杉醇耐药细胞系与其亲代细胞系比较基因组杂交研
究
李维;马艳红;董运鹏;张心丽;谭国林
【期刊名称】《中国肿瘤临床》
【年(卷),期】2011(38)5
【摘要】目的:比较基因组杂交(comparative genomic hybridization,CGH)是一种在荧光原位杂交(fluorescence in situ hybridization,FISH)技术上发展起来的用于检测两个基因组间相对DNA拷贝数的改变(缺失或扩增),并将这些变化在染色体上进行定位的分子细胞遗传学方法.为了解鼻咽癌紫杉醇耐药细胞
(CNE1/Taxol,HNE2/Taxol,5-8F/Taxol)与亲代细胞(CNE1,HNE2,5-8F)在基因组DNA水平上可能存在的差异,以及这种差异在肿瘤获得性耐药产生中的意义,采用CGH技术对鼻咽癌紫杉醇耐药细胞与亲本细胞的基因组DNA进行检测和分析.方法:三株鼻咽癌紫杉醇耐药细胞采用大剂量冲击与剂量逐渐递加相结合的方法诱导而成.采用集落形成实验测定药物的敏感性,利用比较基因组杂交技术(CGH)对耐药细胞和其亲本细胞的基因组DNA进行检测和分析,比较耐药细胞与亲本细胞在染色体扩增与缺失上的共同点和差异.结果:三株鼻咽癌紫杉醇耐药细胞耐药指数分别为8.43、8.27和5.26.鼻咽癌亲本细胞存在广泛的染色体改变,主要表现在3q21-qter,5p13-pter,12和20q11-qter的共同扩增以及10q11-qter,18和X染色体的共同缺失,从亲本细胞系诱导的三株鼻咽癌紫杉醇耐药细胞系表现为3q21-qter,5p13-pter,12,20q11-qter和8q21-qter的共同扩增,无明显共同缺失区域.与亲本细胞共同扩增区域相比,其中最有意义的是8q21-qter区域在三株耐药细胞中出现了新的共同扩增.结论:3q21-qter,5p13-pter,12和20q11-qter的共同扩增
以及10q11-qter,18和X染色体的共同缺失可能与鼻咽癌的发生有关,而8q21-qter染色体扩增可能与鼻咽癌获得性紫杉醇耐药相关,对这些区域的进一步研究,有可能为肿瘤发生及耐药机制研究提供新的线索.%Objective: Comparative genomic hybridization ( CGH ) is a new molecular and cellular technology developed from fluorescence in situ hybridization ( FISH ).It is a molecular cytogenetics method used to examine genomic imbalances, especially the deletion and amplification of chromosomes, and to locate these alterations in certain chromosome regions.To completely understand the possible differences in genomic DNA between three paclitaxel-resistant nasopharyngeal carcinoma cell lines ( CNE1/Taxol, HNE2/ Taxol, 5-
8F/Taxol ) and corresponding parent cells ( CNE1, HNE2, 5-8F ) which were sensitive to paclitaxel medication, and the significance of the differences in nasopharyngeal carcinoma acquired drug-resistance, the genomic DNA of three paclitaxel-resistant nasopharyngeal carcinoma cell lines and their parent cell lines were detected and analyzed using comparative genomic hybridization ( CGH ).Methods: The three paclitaxel-resistant nasopharyngeal carcinoma cell lines ( CNE1/Taxol, HNE2/Taxol, 5-8F/Taxol ) were created by combining high-dose pulse therapy in the parent cells with stepwise dose increments of paclitaxel.The resistance index was determined by colony formation.Cell CGH was performed on paclitaxel-resistant nasopharyngeal carcinoma cell lines and the parent cell lines to explore the changes in chromosomal DNA regions.Results: The resistance indices of the three paclitaxel-resistant nasopharyngeal carcinoma cell lines ( CNE1/Taxol, HNE2/Taxol, 5-8F/Taxol ) were 8.43, 8.27 and 5.26,
respectively.There were extensive chromosomal changes in the three parent cell lines when compared to normal genomic DNA, mainly seen in the co-amplification of 3q21 -qter, 5p13-pter, 12 and 20qll-qter, and the common deletion of 10q11-qter, 18 and X in all three parent cell
lines.However, the three paclitaxel-resistant cell lines showed a relatively normal karyotype with changes mainly in the co-amplification of 3q21-qter, 5p13-pter, 12, 20qll-qter and pared with the common amplifications in parent cell lines, a new co-amplification of 8q21-qter was detected in the three paclitaxel-resistant nasopharyngeal carcinoma cell lines.Conclusion: Co-amplification of 3q21-qter, 5p13-pter, 12 and 20 qll-qter, and deletion of 10q11-qter, 18, and X may be associated with nasopharyngeal carcinoma.Chromosomal amplification of 8q21-qter may be related to paclitaxel-resistance in nasopharyngeal carcinoma cell lines.Further studies on these chromosome regions may supply new clues on the occurrence of nasopharyngeal carcinoma and the mechanism of acquired resistance of nasopharyngeal carcinoma to paclitaxel.
【总页数】5页(P241-245)
【作者】李维;马艳红;董运鹏;张心丽;谭国林
【作者单位】中南大学湘雅三医院耳鼻喉头颈外科,长沙市410013;中南大学湘雅三医院耳鼻喉头颈外科,长沙市410013;中南大学湘雅三医院耳鼻喉头颈外科,长沙市410013;中南大学湘雅三医院耳鼻喉头颈外科,长沙市410013;中南大学湘雅三医院耳鼻喉头颈外科,长沙市410013
【正文语种】中文
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