摘要
目的 观察经动脉插管导入肿瘤坏死因子α(TNF α)和白细胞介素 2 (IL 2 )重组腺病毒对转移性大鼠肝癌模型的治疗作用。方法 用 2 93细胞扩增人TNF α(以下简称TNF)和IL 2重组腺病毒 ,并测定病毒滴度 ;取大鼠乳腺癌细胞株 (Walker 2 5 6 )转染至肝脏的荷瘤大鼠动物模型 ,经肝固有动脉分别注入不同剂量的重组腺病毒 ,首先确定人肿瘤坏死因子 (hTNF)基因的最适用量 ;然后分为hTNF组 ,人IL 2 (hIL 2 )组 ,hTNF +hIL 2组 ,病毒对照组 (LacZ组 )和培养液对照组进行治疗 ,观察大鼠生存期。结果 所制备的人TNF α和IL 2重组腺病毒滴度为 2× 10 9pfu/ml和 2 .1× 10 9pfu/ml。经肝固有动脉注射肿瘤坏死因子重组腺病毒 (Ad .hTNF)的适宜剂量为 1.0× 10 9pfu。治疗结果显示 ,单独注射TNF α或IL 2重组腺病毒能有效延长转移性肝癌大鼠的存活期 ;这两种重组腺病毒单独使用时 ,治疗效果之间存在显著性差异 ;联合应用这两种重组腺病毒比单一使用TNF α或IL 2重组腺病毒能更有效地延长荷瘤大鼠的存活期。结论 经肝动脉插管注射目的基因重组腺病毒 ,可能是基因治疗肿瘤的一种较为有效的途径 。
Objective To investigate the therapeutic effects of TNF and IL 2 recombinant adenoviruses via intra arterial injection on metastatic liver cancer in rat model. Methods Recombinant adenoviruses harboring hTNF α or hIL 2 gene were amplified in 293 cells and subjected to titration by the pathogenetic effects on 293 cell. The rats bearing metastatic liver cancer of Walker 256 breast carcinoma were randomly grouped and administered via gastra intestinal artery with hTNF α recombinant adenoviruses alone, or hIL 2 recombinant adenoviruses alone, or at the dose of 1.0×10 9 pfu/rat. The therapeutic effects were observed including their survival time. Results The prepared recombinant adenoviruses of hTNF α and hIL 2 were with the titers of 2.0×10 9 pfu/ml and 2.1×10 9 pfu/ml, respectively. 1.0 ×10 9 pfu hTNF was the proper dose. Administration of hTNF α or hIL 2 recombinant adenoviruses via hepatic artery could extend the survival time of metastatic liver cancer bearing rats, with the better therapeutic effects achieved by combinatorial administration of these two adenoviruses. Conclusion Arterial administration of adenoviruses may be an effective approach to targeted immunogene therapy for cancer.
出处
《中华放射学杂志》
CAS
CSCD
北大核心
2000年第10期666-669,共4页
Chinese Journal of Radiology
基金
国家"九五"科技攻关计划资助项目!(96 90 6 0 1 2 0 )
关键词
转移性肝癌
经肝动脉插管注射
重组腺病毒
Animal testing alternatives
Radiology, interventional
Interleukin 2
Tumor necrosis factor
Genetic vectors
Adenoviridae
