Long-term gene therapy with Del1 fragment using nonviral vectors in mice with explanted tumors.
Long-term gene therapy with Del1 fragment using nonviral vectors in mice with explanted tumors.
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DOI：
10.2147/ott.s90801
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发表时间：
2016
影响因子：
4
通讯作者：
Hidai C
中科院分区：
文献类型：
--
作者：
Kitano H;Mamiya A;Ishikawa T;Egoshi K;Kokubun S;Hidai C
使用非病毒载体的癌症基因治疗在长时间的治疗中是有用的，因为这种载体既安全又便宜，因此可以重复使用。有报道称，在小鼠移植瘤模型中，用Del1的E3C1片段进行基因治疗可以改善预后。本研究旨在分析反复非病毒基因转移对E3C1细胞的长期影响。人鳞状细胞癌SCCKN细胞移植瘤的小鼠接受了编码E3C1的质粒治疗。每周用一种转染剂局部注射质粒。用模拟DNA处理的对照组小鼠在第18天开始实施安乐死，因为肿瘤已经长到了体重的15%以上，到第43天他们都已经死亡。另一方面，接受E3C1治疗的十只小鼠中有两只肿瘤已经消失。其余8只小鼠在第46天开始实施安乐死，10只小鼠中有8只在第197天前实施了安乐死。治疗18天后，对照组肿瘤体积为2,804±829 mm~3，E3C1小鼠为197±159 mm~3。组织化学研究显示，与对照组相比，E3C1处理组的肿瘤细胞凋亡率增加。E3C1诱导的细胞形态改变和聚合化肌动蛋白减少表明细胞与基质的黏附受到干扰。在SCCKN细胞的体外研究中，与对照细胞相比，在培养细胞中长期给予E3C1重组蛋白可以减少癌细胞的非黏附生长。这些数据表明，E3C1处理可诱导失巢。
Cancer gene therapy using nonviral vectors is useful for long periods of treatment because such vectors are both safe and inexpensive, and thus can be used repeatedly. It has been reported that gene therapy with an E3C1 fragment of Del1 in a mouse explanted tumor model improved prognosis. The present study aimed to analyze the long-term effects of repeated non-viral gene transfer of E3C1. Mice with explanted tumors of SCCKN cells, a human squamous carcinoma, were treated with a plasmid encoding E3C1. Plasmids were injected locally every week using a transfection reagent. Control mice treated with mock DNA started to be euthanized on day 18, because the tumors had grown to over 15% of the body weight, and all of them had died by day 43. On the other hand, the tumors in two of ten mice treated with E3C1 had disappeared. The other eight mice started to be euthanized on day 46 and eight of ten mice had been euthanized by day 197. After 18 days of therapy, the tumor volume of control mice was 2,804±829 mm3 and that of the E3C1 mice was 197±159 mm3. Histochemical studies showed enhanced apoptosis in the E3C1-treated tumors, as compared with controls. Changes in cell morphology and decreased polymerized actin induced by E3C1 indicated disturbed cell adhesion to the matrix. In in vitro studies of SCCKN cells, prolonged administration of an E3C1 recombinant protein to cultured cells reduced adhesion-independent growth of cancer cells, as compared with control cells. These data suggest that E3C1 treatment induces anoikis.