野生型p53基因提高肝癌细胞化疗药物敏感性的实验研究  

Research on reversal effects of wild-type p53 on drug-resistant hepatoma cells

作　　者：梁云[1] 陆斌[1] 李晓冬[1] 王华菁[1] 崔贞福[1] 郭亚军[1] 刘彦君[1] 

机构地区：[1]第二军医大学国际合作肿瘤研究所,上海200433

出　　处：《第二军医大学学报》2002年第1期24-25,共2页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金资助项目 ( 39880 0 47和395 0 0 174)

摘　　要：目的 :研究野生型 p5 3(wtp5 3)提高肝癌细胞化疗药物敏感性的作用。 方法 :采用 p5 3基因型不同的三种人肝癌细胞株 Hep G2 (部分 wtp5 3)、Hep3B(p5 3- / - )和 PL C/ PRF/ 5 (mtp5 3) ,观察携 wtp5 3基因的重组腺病毒联合化疗药物争光霉素(bleomycin,bleo)、丝裂霉素 (mitomycin,m ito)或甲氨蝶呤 (m ethotrexate,meth)对肝癌细胞的杀伤效应。 结果 :Hep G2、Hep3B和 PL C/ PRF/ 5分别耐受 6 0 0μg/ ml bleo、10 0μg/ ml m ito或 10 0 0μg/ ml m eth,但转入 wtp5 3基因后再使用上述质量浓度范围的化疗药物 ,则肝癌细胞出现了明显的被杀伤效应。 结论 :wtp5 3基因能提高肝癌细胞对化疗药物的敏感性 ,wtp5 3基因联合化疗药物治疗可望开辟克服肝癌耐药的新途径。Objective: To investigate the reversal effects of p53 on the drug-resistant hepatoma cells. Methods: The 3 hepatoma cell lines with different status of p53 were treated with bleomycin, mitomycin or methotrexate following infection with wtp53 via a recombinant adenovirus. Results: HepG2(wtp53), Hep3B(p53-/-) and PLC/PRF/5 (mtp53) were not sensitive to 600 μg/ml of bleo, 100 μg/ml of mito or 1 000 μg/ml of meth. But when introduced by wtp53 and retreated with same concentration of above drugs, the hepatoma cell growth were markedly suppressed. Conclusion: wtp53 gene transfer and chemotherapy can reverse the hepatoma cell's drug resistance. Gene therapy using wtp53-expressing adenovirus in combination with a chemotherapy may be an attractive strategy for hepatoma.

关 键 词：P53基因 肝肿瘤 基因治疗 药敏试验 

分 类 号：R735.7[医药卫生—肿瘤]