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携带p53基因增殖性腺病毒影响肝癌细胞对化疗药物的敏感性
段纪成,钱其军,岳海燕,沈丽,丁光辉,杨家和,DUANJi-cheng,QIANQi-jun,YUEHai-yan,SHENLi,DINGGuang-hui,YANGJia-he
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摘要:
目的:研究携带p53基因增殖性腺病毒CNHK600-p53载体能否增加肝癌细胞株对化疗药物的敏感性.方法:构建携带p53基因增殖性腺病毒CNHK600-p53载体,采用四甲基偶氮唑盐法(methylthiazolyl tetrazolium assay,MTT),观察并比较单用化疗药物[5-氟尿嘧啶(fluorouracil,5-Fu)、丝裂霉素(mitomycin,MMC)和表柔比星(epirubicin,EPI)]、单用CNHK600-p53和CNHK600-p53联合上述化疗药物对肝癌细胞株BEL-7404的杀伤效应.结果:肝癌细胞株BEL-7404在5-Fu浓度为100μg/ml时细胞抑制率为(47±3)%,MMC浓度为1μg/ml时细胞抑制率为(20±4)%,EPI浓度为2.5 μg/ml时细胞抑制率为(73±2)%,联合CNHK600-p53(MOI=10)后上述浓度的化疗药物细胞抑制率分别增高为(59±4)%、(44±4)%和(86±2)%(率的U检验,P<0.01).结论:携带p53基因的CNHK600-p53能提高肝癌细胞株BEL-7404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.
关键词:  p53基因、肝肿瘤、抗药性,肿瘤、基因疗法
DOI:10.3724/SP.J.1008.2006.00628
投稿时间:2006-01-10修订日期:2006-04-10
基金项目:
Effect of replicating adenovirus harboring p53 gene on chemosensitivity of hepatocarcinoma cell line
段纪成,钱其军,岳海燕,沈丽,丁光辉,杨家和,DUAN Ji-cheng,QIAN Qi-jun,YUE Hai-yan,SHEN Li,DING Guang-hui,YANG Jia-he
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Abstract:
Objective: To construct a replicating adenovirus vector CNHK600-p53 carrying p53 gene and investigate its effect on the chemosensitivity of hepatocarcinoma cell line. Methods: Chemotherapy of hepatocarcinoma cells BEL-7404 were carried out using Fluorouracil, Mitomycin, Epirubicin, CNHK600-p53, CNHK600-p53 + Fluorouracil, CNHK600-p53 + Mitomycin, and CNHK600-p53 + Epirubicin, separately. MTT assay was used to evaluate the killing effects after therapy. Resuits: The inhibition rate on BEL-7404 cells was(47±3)% when using 100 μg/ml 5-Fu, was (20±4)% when using 1 μg/ml MMC, and was (73±2)% when using 2.5 μg/ml EPI. The inhibition rates of BEL-740 cells in CNHK600-p53(MOI= 10) + Fluorouracil (100 μg/ml), CNHK600-p53(MOI=10) + Mitomycin (1 μg/ml), and CNHK600-p53 (MOI= 10)+ Epirubicin (2.5 μg/ml) groups were (59±4) %, (44±4) % and (86±2) %, respectively (P〈0.01). Conclusion: Adenovirus CNHK600- p53 carrying p53 gene can enhance chemosensitivity of BELT404 hepatocarcinoma cell line. Gene therapy using adenovirus CNHK600-p53 in combination with chemotherapy may be a new strategy for hepatocarcinoma treatment.
Key words:  p53 gene  liver neoplasms  drug resistance,neoplasm  gene therapy