权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Gene Therapy for Colon Cancer with Adenoviral Vector Expressing Tumor Suppressor p53 Gene

表达肿瘤抑制p53基因的腺病毒载体对结肠癌的基因治疗

基本信息

批准号：
07671393
负责人：
HIZUTA Akio
金额：
$ 1.47万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671393/
关键词：
p53 Gene Therapy Colon Cancer Cisplatin アデノウイルスベクターウイルスベクター

项目摘要

The alteration of wild-type p53 gene by mutations, deletions, or rearrangements is a major factor in the development of human colon cancer. Recent studies have demonstrated that p53 might be an essential component of the cytotoxic pathway triggered by DNA-damaging stimuli such as chemotherapeutic agents and ionizing radiation. We examined the antitumor effect of adenovirus-mediated wild-type p53 gene transfer in combination with a chemotherapeutic drug on human colon cancer cell line WiDr, which has a homozygous mutated p53 gene. The treatment with a chemotherapeutic drug, cisplatin, following the infection of a replication-deficient, recombinant adenoviral vector expressing wt-p53 (termed AdCMV p53) significantly suppressed the growth of WiDr cells compared to any single treatments. To evaluate the in vivo efficacy of AdCMV p53 and cisplatin given in a sequential combination, WiDr cells were subcutaneously inoculated in nu/nu mice, and after 3 days AdCMV p53 was subcutaneously injected into the area where tumor cells were implanted followed by intraperitoneal administration of cisplatin. Analysis of initial growth inhibition at 21 days demonstrated a profound, therapeutic cooperativity, although AdCMV p53 alone or cisplatin alone showed a modest slowing of the tumor growth. These results suggest that the gene therapy using wt-p53-expressing a denovirus in combination with a chemotherapeutic DNA-damaging drug is a useful strategy for human colon cancer therapy.

野生型P53基因的突变、缺失或重排是人类结肠癌发生发展的重要因素。最近的研究表明，P53可能是化疗药物和电离辐射等DNA损伤刺激所触发的细胞毒途径的重要组成部分。我们检测了腺病毒介导的野生型p53基因转移联合化疗药物对突变了p53基因的人结肠癌细胞株WiDR的抗肿瘤作用。在感染复制缺陷的重组腺病毒载体wt-P53(称为AdCMV P53)后，化疗药物顺铂显著抑制了WiDR细胞的生长。为了评价AdCMV-P53与顺铂序贯给药的体内疗效，将WiDR细胞接种于nu/nu小鼠皮下，3d后将AdCMV-P53注射到肿瘤细胞种植部位，然后腹腔注射顺铂。对第21天的初始生长抑制的分析表明，尽管单独使用AdCMV P53或单独使用顺铂对肿瘤生长有轻微的减缓作用，但仍具有深刻的治疗协同性。这些结果表明，使用表达wt-p53的逆转录病毒与化疗DNA损伤药物相结合的基因治疗是一种有用的结肠癌治疗策略。