增殖性腺病毒CNHK600-p53可增强肝癌细胞株SMMC7721对化疗药物的敏感性  

RESEARCH ON REVERSAL EFFECTS OF REPLICATION-selective adenovirus CNHK600-p53 ON DRUG-RESISTANT HEPATOMA CELL LINE SMMC7721

作　　者：段纪成[1] 钱其军[1] 陈洁[2] 钱炎珍[1] 刘凯[1] 戴炳华[1] 杨家和[1] 

机构地区：[1]第二军医大学东方肝胆外科医院,上海200438 [2]兰州军区兰州总医院

出　　处：《肝胆外科杂志》2006年第4期290-293,共4页Journal of Hepatobiliary Surgery

摘　　要：目的构建携带p53基因新型增殖性腺病毒CNHK600-p53,研究其是否增加肝癌细胞株对化疗药物的敏感性。方法采用四甲基偶氮唑盐(m ethylth iazolyl tetrazolium assay,MTT),观察化疗药物5-氟尿嘧啶(F luorourac il,5-Fu)、丝裂霉素(M itomyc in,MMC)和表阿霉素(Ep irub ic in,EPI)组与携带p53基因的重组腺病毒CNHK600-p53联合上述化疗药物组对肝癌细胞株SMMC7721的杀伤效应,同时观察其是否优于Ad-p53。结果单用CNHK600-p53或Ad-p53对肝癌细胞SMMC7721的杀伤效果无明显差别;肝癌细胞株SMMC7721在5-Fu浓度为100 ug/m l时细胞抑制率为58%,MMC浓度为2.5 ug/m l时细胞抑制率为50%,EPI浓度为1.25ug/m l时细胞抑制率为57%,但转入CNHK600-p53(MO I=10)后再使用上述浓度的化疗药物,细胞抑制率分别为76%、60%和62%。结论单用CNHK600-p53或Ad-p53对肝癌细胞SMMC7721的杀伤效果无明显差别,携带p53基因的CNHK600-p53能提高肝癌细胞株SMMC7721对化疗药物的敏感性,CNHK600-p53联合化疗药物治疗可望开辟克服肝癌耐药的新途径。Objective The construct of a new type replication-selective adenovirus CNHK600-p53 and investigate the reversal effects of CNHK600-p53 on the drug resistant hepatoma cell. Methods The SMMC7721 hepatoma cell line were treated with Fluorouracil, Mitomycin and Epirubicin following infection with CNHK600-p53 or alone with these same chemodrugs or CNHK600-p53 ; Then use methylthiazolyl tetrazolium assay （MTT） method investigate its cytolysis ; Also investigate if CNHK600-p53 is better than Ad-p53 alone use. Results CNHK600-p53 is not better than Ad-p53 when used only; The SMMC7721 hepatoma cell line were not sensitive to these chemodrugs. 5-Fu at concentration of 100ug/ml, the rate of resrtrained SMMC7721 cell is 58% ; MMC at concentration of 2. 5ug/ml, the rate of resrtrained SMMC7721 cell is 50% ; EPI at concentration of 1.25ug/ml, the rate of resrtrained SMMC7721 cell is 57%. But when introduced by CNHK600-p53 （MOI = 10）and retreated with same concentration of above drugs, The rate of resrtrained SMMC7721 cells are 76% ,60% and 72%. Conclusion CNHK600-p53 is not better than Ad-p53 when used only in the SMMC7721 hepatoma cell line. CNHK600-p53 transfer and chemotherapy can reverse the SMMC7721 hepatoma cell＇s drug resistance. Gene therapy using CNHK600-p53 in combination with chemotherapy may be an attractive strategy for hepatoma.

关 键 词：基因 P53 肝肿瘤 抗药性 基因疗法 

分 类 号：R735.7[医药卫生—肿瘤]