人小细胞肺癌多药耐药细胞系H446/VP的建立及其生物学性状  

Establishment and characterization of an etoposide-resistant human small cell lung cancer cell line H446/VP

作　　者：张会军[1] 阎蕴力[2] 郑力芬[2] 樊平[2] 

机构地区：[1]河北医科大学第一医院胸外科,石家庄050031 [2]河北医科大学基础所细胞生物室

出　　处：《肿瘤》2004年第3期233-236,共4页Tumor

摘　　要：目的　建立人小细胞肺癌足叶乙甙多药耐药细胞系H4 4 6 /VP ,进行生物学性状的研究 ,分析其耐药特点。方法　采用高浓度反复间歇诱导的方法 ,建立人小细胞肺癌足叶乙甙多药耐药细胞系H4 4 6 /VP ,并对其光镜形态、超微结构、生长特点进行了研究 ;流式细胞术对细胞周期分布的变化进行了分析 ;采用MTT法分析其耐药谱。结果　H4 4 6 /VP的光镜形态与亲代细胞相似 ,但透射电镜畸形核多见 ,胞浆内有较多的线粒体、核糖体及滑面内质网 ;H4 4 6 /VP的生长速度减慢 ,细胞倍增时间为 35 .7h ,比亲代细胞系长 7.9h ;其细胞周期分布G0 /G1期细胞增多 ,为 6 5 .12± 1.6 7% ,G2 /M细胞为 3.99± 1.4 9% ,较亲代细胞减少 ;MTT法耐药谱分析表明 ,该细胞系对VP 16的耐药倍数为 17.8,除此之外 ,该细胞系对ADR、NVT、VCR、MMC、CDDP等药物也产生了交叉耐药 ,耐药倍数分别为 8.9、5 .4、4 .7、4 .4、1.7,对 5 FU、MTX、CTX仍保持敏感。结论　本实验建立了稳定的人小细胞肺癌多药耐药细胞系H4 4 6 /VP 。Objective To establish an etoposide resistant human small cell lung cancer cell line H446/VP and study its biological characteristics. Methods H446/VP cell line was obtained by exposing at intervals and repeatedly to high dose of etoposide for 7 months. The morphological feature, ultrastructure and growth characters were examined. Flow cytometry was used to evaluate the cell cycle distribution of H446/VP and its parental cell line. MTT assay was used to measure the cross resistant profile of H446/VP cells.Results Under light microscope, H446/VP cells was similar with H446 cells stained by hematoxylin and eosin. While observed by transmission electron microscope, there were more malformed nuclei, abundant mitochondria, ribosomes and endoplasmic reticular in H446/VP cells. H446/VP cells grew more slowly than H446 cells and their population double time was 7.9 hours, which was longer than H446 cell line. Cell cycle distribution of H446/VP cells has changed compared with parental cells. The percentage of cells in G 0/G 1 phase increased to 65.12±1.67%, while the percentage of cells in G 2 /M phase decreased to 3.99±1.49%. The resistance index of H446/VP cells to etoposide was 17.8 and the cells showed various cross resistance to ADR, NVT, VCR, MMC and CDDP, the resistance indexes were 8.9, 5.4, 4.7, 4.4 and 1.7, respectively. The cells remain sensitive to 5 Fu, MTX, CTX, and so on. Conclusion A multidrug resistance cell line H446/VP from human small cell lung cancer is established. It can be used for further experiments.

关 键 词：小细胞肺癌 多药耐药 H446/VP细胞 生物学性状 超微结构 

分 类 号：R734.2[医药卫生—肿瘤] R730.3[医药卫生—临床医学]