封闭ERCC1基因表达对卵巢癌细胞耐药的影响

被引:12
作者
李体远
Jing Jie Yu
Eddie Reed
机构
[1] 暨南大学医学院附二院深圳市人民医院临床医学研究中心
[2] West Virginia University
[3] Mary Babb Randolph Cancer Center
[4] Morgantown
[5] West Virginia -
[6] West Virginia - 深圳
关键词
ERCC1/DNA损伤修复; 耐药/顺铂; 卵巢癌;
D O I
暂无
中图分类号
R737.31 [卵巢肿瘤];
学科分类号
100214 ;
摘要
目的:探讨通过封闭ERCC1基因表达干扰DNA损伤修复路径及其对卵巢癌细胞对铂类药物耐药性的影响。方法:构建ERCC1基因反义表达载体,转染人卵巢癌细胞A2780及A2780/CF70,采用Northern杂交及Western Blot分析人卵巢癌细胞内ERCC1基因RNA及蛋白表达水平变化;利用荧光素酶报告基因系统观察宿主细胞对DNA损伤的修复作用;采用MTT实验研究细胞对铂类药物耐药性的影响。结果:卵巢癌细胞转染反义ERCC1基因后,ERCC1基因转录水平、蛋白表达水平明显下降。荧光素酶报告基因系统结果证明,宿主细胞的DNA修复活性下降。MTT实验表明,伴随ERCC1基因表达水平下降,细胞对顺铂的耐药性降低。结论:转染ERCC1反义基因显著影响宿主细胞的核苷酸切除修复,影响细胞对顺铂的耐药性。
引用
收藏
页码:92 / 95
页数:4
相关论文
共 9 条
[1]  
ERCC1 expression as a molecular marker of cisplatin resistance in human cervical tumor cells. Britten RA,Liu D,Tessier A,et al. International Journal of Cancer . 2000
[2]  
Human DNA repair genes. Wood RD,Mitchell M,Sgouros J,et al. Science . 2001
[3]  
Cisplatin-induced apoptosis in 43-3B and 27-1 cells defective in nucleotide excision repair. Dunkern TR,Fritz G,Kaina B. Mutation Research . 2001
[4]  
Enhanced host cell reactivation capacity and expression of DNA repair genes in human breast cancer cells resistant to bi-functional alkylating agents. Yen L,Woo A,Christopoulopoulos G,et al. Mutation Research . 1995
[5]  
Elevated DNA repair capacity is associated with intrinsic resistance of lung cancer to chemotherapy. Zeng-Rong N,Paterson J,Alpert L,et al. Cancer Research . 1995
[6]  
Increased nucleotide excision repair in cisplatin-resistant ovarian cancer cells: Role of ER-CC1-XPF. Ferry KV,Hamilton TC,Johnson SW. Biochemical Pharmacology . 2000
[7]  
ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy. Metzger R,Leichman CG,Danenberg KD,et al. Journal of Clinical Oncology . 1998
[8]  
Expression of genes involved in nucleotide excision repair and sensitivity to cisplatin and melphalan in human cancer cell lines. Damia G,Guidi G,D’lncalci M. European Journal of Cancer . 1998
[9]  
Platinum-DNA adduet, nucleotide excision repair and platinum based anti-cancer chemotherapy. Reed E. Cancer Treatment Reviews . 1998