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Growth inhibition of the pulmonary metastatic tumors by systemic delivery of the p27 kip1 gene using lyophilized lipid‐polycation‐DNA complexes
Author(s) -
Sun Xun,
Zhang HongWei,
Zhang ZhiRong
Publication year - 2009
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1322
Subject(s) - cancer research , genetic enhancement , gene delivery , in vivo , growth inhibition , liposome , cationic liposome , h&e stain , heparanase , microbiology and biotechnology , chemistry , cancer , cell growth , medicine , biology , pathology , metastasis , immunohistochemistry , gene , biochemistry
Background p27 kip1 (p27), a cyclin‐dependent kinase inhibitor (CDKI), is an important regulator of cell cycle progression and a putative tumor suppressor gene, and plays an important role in the inhibition of genesis and progression of several kinds of cancers. The present study aimed to evaluate the anti‐tumor effects of p27 gene therapy by a nonviral gene delivery strategy on pulmonary metastatic tumors. Methods A recombinant plasmid composed of a p27 sequence was constructed and identified; it was then formulated with condensing agent protamine sulfate and entrapped into cationic liposomes. The resulting lipid‐polycation‐DNA complexes (LPD) were prepared into lyophilized forms. 5 × 10 5 of CT26 colorectal adenocarcinoma cells were inoculated into female Balb/c mice via the tail vein to establish lung tumor models. On the second day, mice were randomly divided into six groups for different intravenous treatments: phosphate‐buffered saline, empty liposomes, naked pDNA, LPD‐p27 kip1, Cisplatin (DPP), and LPD‐p27 kip1 plus DPP, respectively. Results The growth curve of tumor and the growth inhibition rate of tumor showed that p27‐LPDs could prolong the lifespan of the mice significantly, whereas the combination of p27‐LPDs and DPP could further prolong the lifespan of the tumor‐bearing animals. The histology of tumors examined by hematoxylin and eosin staining indicated that p27‐LPDs had a stronger inhibition effect. Significant expression of p27 was detected in tumors using an immunohistochemical technique. Conclusions Lyophilized LPD could be used as a potential in vivo gene delivery carrier for lung cancer gene therapy. Copyright © 2009 John Wiley & Sons, Ltd.