Polyethylenimine-mediated gene transfer into pancreatic tumor dissemination in the murine peritoneal cavity
Polyethylenimine-mediated gene transfer into pancreatic tumor dissemination in the murine peritoneal cavity
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DOI：
10.1038/sj.gt.3301435
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发表时间：
2001-04-01
期刊：
影响因子：
5.1
通讯作者：
Yoshida, T
中科院分区：
文献类型：
--
作者：
Aoki, K;Furuhata, S;Yoshida, T
虽然癌细胞的腹膜播散常发生在胰腺癌、胃癌或卵巢癌的晚期，但尚无有效的治疗方法。阳离子脂质介导的基因转移到腹膜传播可能提供安全治疗的前景，但关于基因转移的效率和特异性，载体需要改进。在本研究中，评估了质粒DNA：聚乙烯亚胺（PEI）复合物腹腔注射作为腹膜传播的基因传递系统。荧光素酶和-半乳糖苷酶基因作为标记基因。PEI在体内比本研究中检测的阳离子脂质更有效，并且转基因在肿瘤中优先表达。虽然PCR分析显示注射的DNA被输送到各个器官，但在基因转移6个月后，分布的DNA就无法检测到了。血液化学和组织学分析显示注射小鼠无明显毒性。本研究表明，腹腔注射DNA:PEI是一种很有前途的传递方法，可以将基因转导到腹腔弥散性癌结节中。
Although peritoneal dissemination of cancer cells often occurs at the advanced stages of pancreatic, gastric or ovarian cancers, no effective therapy has been established. Cationic lipid-mediated gene transfer into peritoneal dissemination may offer a prospect of safe therapies, but vector improvements are needed with regard to the efficiency and specificity of the gene transfer. In this study, the intraperitoneal injection of plasmid DNA:polyethylenimine (PEI) complexes into mice was evaluated as a gene delivery system for the peritoneal disseminations. The luciferase and beta -galactosidase genes were used as marker genes. PEI was more efficient than the cationic lipids examined in this study in vivo, and the transgene was preferentially expressed in the tumors. Although PCR analysis showed that the injected DNA was delivered to various organs, the distributed DNA became undetectable by 6 months after the gene transfer. Blood chemistry and histological analysis showed no significant toxicity in the injected mice. This study demonstrated that the intraperitoneal injection of DNA:PEI is a promising delivery method to transduce a gene into disseminated cancer nodules in the peritoneal cavity.