Louis M-H, Dutoit S, Denoux Y, Erbacher P, Deslandes E, Behr J-P, Gauduchon P, Poulain L
Groupe Régional d'Etude sur le Cancer (GRECAN), Unité 'Biologie et Thérapies Innovantes des Cancers Localement Agressifs' et, Centre F. Baclesse, Caen cedex, France.
Cancer Gene Ther. 2006 Apr;13(4):367-74. doi: 10.1038/sj.cgt.7700893.
Linear polyethylenimine (L-PEI) is an efficient transfection agent for ovarian carcinoma cells in vitro and ex vivo. In the present work, we go a step further and evaluate the efficacy of L-PEI in human ovarian tumor nodes developed in mice. PEI/DNA complexes were administered intraperitoneally instead of intravenously to avoid sequestering of complexes in the lung and liver and to allow transfection of nonvascularized tumor nodes. Plasmid biodistribution was studied by PCR and gene expression was characterized using complementary luciferase and beta-galactosidase assays. Intraperitoneal (i.p.) injection of L-PEI/DNA complexes allowed the straightforward distribution of plasmid in the whole peritoneal cavity. Gene expression occurred in many organs, but tumor nodes appeared as preferential sites for transgene expression. The i.p. delivery route allowed repeated injections and administration of large amounts of DNA (up to 400 mug) without signs of toxicity, even for doses well beyond the intravenous lethal dose. Transgene expression was dose-dependent and transient. However, multiple injections allowed its persistence to increase. These results provide encouraging elements towards the development of PEI-based gene therapy protocols for the treatment of advanced stage ovarian carcinoma.
线性聚乙烯亚胺（L-PEI）在体外和离体条件下是一种用于卵巢癌细胞的高效转染剂。在本研究中，我们更进一步，评估了L-PEI对小鼠体内生长的人卵巢肿瘤结节的作用效果。将PEI/DNA复合物经腹腔注射而非静脉注射，以避免复合物在肺和肝脏中被截留，并使非血管化的肿瘤结节能够被转染。通过PCR研究质粒的生物分布，并使用互补的荧光素酶和β-半乳糖苷酶测定法对基因表达进行表征。腹腔内（i.p.）注射L-PEI/DNA复合物可使质粒直接分布于整个腹腔。许多器官都出现了基因表达，但肿瘤结节是转基因表达的优先位点。腹腔给药途径允许重复注射和给予大量DNA（高达400μg），即使剂量远超静脉致死剂量，也没有毒性迹象。转基因表达呈剂量依赖性且是短暂的。然而，多次注射可使其持续时间增加。这些结果为开发基于PEI的基因治疗方案用于治疗晚期卵巢癌提供了令人鼓舞的依据。
