红霉素逆转人胃癌细胞株多药耐药性的研究  

Reversal of Drug Resistance by Erythromycin on a Doxorubicin-resistant Human Gastric Cancer Cell Line

作　　者：葛成华[1] 王世伟[1] 乔世铭[1] 顾文军[1] 潘芳芳[1] 林言箴 

机构地区：[1]上海市杨浦区中心医院普外科,200090 [2]上海消化外科研究所,200025

出　　处：《外科理论与实践》2003年第5期391-393,共3页Journal of Surgery Concepts & Practice

摘　　要：目的:研究以红霉素逆转人胃癌SGC7901/ADM亚株所呈现的多药耐药性。方法:应用递增阿霉素剂量的方法,诱导建立人胃癌细胞耐药亚株。试以红霉素逆转该耐药亚株对阿霉素等抗癌药物的耐药性,以MTT法测定各药之细胞毒作用,用LSAB法检测亲本(SGC7901)与耐药细胞亚株(SGC7901/ADM)之P鄄糖蛋白的表达水平。结果:体外诱导建立之人胃癌细胞耐药亚株SGC7901/ADM,对阿霉素的相对耐受度较亲本细胞SGC7901提高了9.1倍;前者同时对长春新碱、鬼臼乙叉甙呈交叉耐药性,而对丝裂霉素和顺铂则不显示交叉耐药性。红霉素浓度为273、545、1090μmol/L时,均可提高阿霉素、长春新碱、鬼臼乙叉甙对SGC7901/ADM耐药细胞亚株的细胞毒作用。免疫细胞化学研究显示,约86%的耐药亚株表达P鄄糖蛋白,而亲本细胞则均为阴性。结论:非毒性剂量的红霉素可以逆转人胃癌耐药细胞株的耐药性,为临床上胃癌常规化疗方案中加用红霉素提供了实验依据。Objective:Trial to reverse the drug-resistant effect of a doxorubicin-resistant human gastric cancer cell line by erythromycin.Methods:A human gastric cancer cell line resistant to doxorubicin(SGC7901/ADM)was induced in vitro by exposing SGC7901parent cells to progressively higher concentrations of adriamycin.The cytotoxicity of doxorubin,vin-cristine,etoposide,cisplatin and mitomycin on SGC7901/ADM was determined by MTT assay.The expression of P-glyco-protein of SGC7901and SGC7901/ADM was investigated by LSAB.Results:The SGC7901/ADM cells were9.1times more resistant to doxorubicin than the SGC7901parent cells.The SGC7901/ADM exhibited cross-resistance to vincristine and etoposide,but not to mitomycin and cisplatin.Unlike the SGC7901parent cells,about86%of the SGC7901/ADM cells showed a P-glycoprotein positive reaction.Erythromycin at the concentrations of273,545and1090μmol/L was shown by MTT to increase significantly the chemosensitivity of SGC7901/ADM to doxorubin,vincristine and etoposide.Conclusions:Erythromycin in concentrations of273μmol/L to545μmol/L,which is nontoxic to human body in vivo,could reverse multidrug resistance of human gastric cancer cell subline SGC7901/ADM.

关 键 词：红霉素 胃癌 细胞株 多药耐药性 P-糖蛋白 

分 类 号：R735.2[医药卫生—肿瘤] R978.15[医药卫生—临床医学]