Growth inhibition of the pulmonary metastatic tumors by systemic delivery of the p27 kip1 gene using lyophilized lipid-polycation-DNA complexes.
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 x 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.
Sun
Xun
X
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Sichuan, China.
Zhang
Hong-Wei
HW
Zhang
Zhi-Rong
ZR