五种卵巢癌耐药细胞系的建立及其部分耐药相关基因的表达  

Establishment of 5 resistant ovarian cancer cell strains and expression of resistance-related genes

作　　者：栾英姿[1] 李力[1] 黎丹戎[1] 张玮[1] 唐步坚[1] 

机构地区：[1]广西医科大学附属肿瘤医院妇瘤科,南宁530021

出　　处：《中华妇产科杂志》2004年第6期403-407,共5页Chinese Journal of Obstetrics and Gynecology

基　　金：国家自然科学基金资助项目 ( 3 0 0 60 0 84);广西科学基金资助项目 (桂科青 0 2 2 90 0 8)

摘　　要：目的　建立 5种卵巢癌耐药细胞系 ,并比较耐药与其非耐药卵巢癌细胞系之间部分耐药相关基因的表达差异。方法　用卵巢癌细胞系SKOV3、A2 780分别建立顺铂、卡铂、紫杉醇 (商品名 :泰素 )耐药的细胞系SKOV3/DDP、SKOV3/CBP、A2 780 /DDP、A2 780 /CBP、A2 780 /toxol,验证其有关的生物学指标 ;并用RT PCR技术检测耐药与其非耐药卵巢癌细胞系之间部分基因的表达差异。结果　 (1)所有耐药细胞系对相关药物的耐药指数 (RI)较其非耐药细胞系均升高约 3倍或以上 ,并对临床常用的一些化疗药物表现出不同程度的耐受性 ,RI达 2～ 2 0倍 ;耐药细胞的生长速度较其非耐药细胞明显减慢 (P <0 0 1) ;群体倍增时间明显延长 1 4～ 2 4倍 (P <0 0 1) ,但G1、G2 、S期细胞比例无明显改变 (P >0 0 5 ) ;耐药细胞中药物浓度较其非耐药细胞中下降约 2 0～ 8 5倍 (P <0 0 5 )。 (2 )在检测的耐药相关基因中 ,耐药细胞较其非耐药细胞中表达下降的有p5 3、肺耐药蛋白 (LRP 1)、多药耐药相关蛋白 (MRP 1)基因 ,表达升高的有蛋白激酶C(PKC)、拓扑异构酶 (topo)Ⅰ、topoⅡβ基因 ,无明显改变的有谷胱甘肽 S 转移酶 (GST pi)、topoⅡα基因 ,多药耐药蛋白 (MDR 1)基因的表达改变不确定 ,包括升高和下降。Objective To investigate expression difference of several drug resistance related genes between sensitive and resistant ovarian carcinoma cells. Methods Cell lines resistant to cisplatin, carboplatin and taxol were established from ovarian carcinoma cell lines of SKOV3 and A2780, and their biological features were detected. The expressions of several genes related to drug resistance were measured by RT-PCR method. Results (1) The values of resistance index(RI) of resistant cells to relevant drugs were elevated 3 times or more, with different degrees of cross-resistance to several other drugs(RI 2～20). They grew more slowly than primary cells(Td elongated 1.4～2.4 times, P<0.01) without obvious changes in G 1, G 2, and S ratios(P>0.05). Intracellular concentrations of relevant drugs were reduced 2.0～8.5 times in resistant cells(P<0.05). (2) p53, lung resistance protein-1 (LRP-1), multiple drug resistance related protein-1 (MRP-1) genes were expressed at lower levels in resistant cells than in sensitive cells; while protein kinase C (PKC), topoisomerase (topo) Ⅰ, and topo Ⅱ β were expressed higher, no obvious alterations were found concerning glutathione S transferase-pi (GST-pi), and topo Ⅱ α. Expression of multiple drug resistance-1 (MDR-1) gene was either elevated or reduced in different cells. Conclusions The expressions of resistance related genes were widely different in different kinds of resistant cells, suggesting more than one pathway leading to resistance transformation. This adds more difficulties for clinical management.

关 键 词：卵巢肿瘤 培养的肿瘤细胞 抗药性 基因表达 MDR基因 

分 类 号：R737.31[医药卫生—肿瘤]