Targeted chemotherapy against intraperitoneally disseminated colon carcinoma using a cationized gelatin-conjugated HVJ envelope vector
Targeted chemotherapy against intraperitoneally disseminated colon carcinoma using a cationized gelatin-conjugated HVJ envelope vector
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DOI：
10.1158/1535-7163.mct-05-0352
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发表时间：
2006-04-01
影响因子：
5.7
通讯作者：
Kaneda, Y
中科院分区：
文献类型：
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作者：
Mima, H;Yamamoto, S;Kaneda, Y
来源于灭活HVJ颗粒的日本包膜血凝病毒（HVJ-E;仙台病毒）载体可用于在体外和体内将DNA、蛋白质和药物递送到细胞中。HVJ-E能够将抗癌药物博来霉素递送至各种癌细胞系，从而产生比单独施用博来霉素大300倍的细胞毒性。在腹膜扩散结肠癌的小鼠模型中，我们将含有荧光素酶基因的HVJ-E注射到腹膜中。出乎意料的是，在肿瘤沉积物或任何器官内均未观察到荧光素酶基因表达。然而，当与阳离子化明胶（CG）组合时，CG-HVJ-E主要在肿瘤沉积物内产生高水平的荧光素酶基因表达。在将结肠癌细胞引入实验小鼠的腹膜后48小时，将含有或不含有博来霉素的CG-HVJ-E注射到腹腔中。在6次注射博来霉素掺入的CG-HVJ-E后，在40%的检查小鼠中观察到完全反应。所有接受空CG-HVJ-E或单独接受博来霉素的小鼠在将癌细胞引入腹膜后40天内死亡。当具有完全反应的小鼠用来自相同细胞系的结肠癌细胞再次攻击时，没有肿瘤发生。因此，CG-HVJ-E可以抑制癌症的腹膜传播。
The hemagglutinating virus of Japan envelope (HVJ-E; Sendai virus) vector derived from inactivated HVJ particles can be used to deliver DNA, proteins, and drugs into cells both in vitro and in vivo. HVJ-E is capable of delivering bleomycin, an anticancer drug, to various cancer cell lines, thereby producing 300-fold greater cytotoxicity than administration of bleomycin alone. In a mouse model of peritoneally disseminated colon cancer, we injected HVJ-E containing the luciferase gene into the peritoneum. Unexpectedly, luciferase gene expression was not observed within the tumor deposits or any organs. However, when combined with cationized gelatin (CG), CG-HVJ-E produced a high level of luciferase gene expression primarily within the tumor deposits. Forty-eight hours after introducing colon cancer cells into the peritoneum of experimental mice, CG-HVJ-E with or without bleomycin was injected into the abdominal cavity. Following six injections of bleomycin-incorporated CG-HVJ-E, complete responses were observed in 40% of the mice examined. All of the mice that received either empty CG-HVJ-E or bleomycin alone died within 40 days of having cancer cells introduced into the peritoneum. When the mice with complete responses were rechallenged with colon cancer cells from the same cell line, no tumors developed. Thus, CG-HVJ-E may suppress peritoneal dissemination of cancer.