The enhanced antitumor effects of biodegradable cationic heparin-polyethyleneimine nanogels delivering HSulf-1 gene combined with cisplatin on ovarian cancer

作者: PING LIU , MALING GOU , TAO YI , XIAORONG QI , CHUAN XIE

DOI: 10.3892/IJO.2012.1558

关键词: Ovarian cancerCarcinogenesisCancerIn vivoCell cycleBiologyAngiogenesisOncogeneCancer researchCisplatin

摘要: HSulf-1 (heparan sulfate 6-O-endosulfatase 1), a commonly downregulated gene in the majority of ovarian cancer cell lines, has been identified to play an important role regulating tumorigenesis. Our previous studies demonstrated that could inhibit angiogenesis and tumorigenesis vivo. The employment polymeric nanoparticles deliver functional holds much promise as effective therapeutic strategy against cancer. To develop more therapy, this study, we investigated antitumor effect heparin-polyethyleneimine (HPEI) nanogels delivering combined with cisplatin (DDP) on Expression vitro vivo was determined by reverse transcription polymerase chain reaction (RT-PCR) western blot analysis. A SKOV3 intraperitoneal carcinomatosis model nude mice established assess efficacy. Mice were treated NS, pEP/HPEI complexes, pHSulf-1/HPEI DDP or plus DDP, respectively. Intraperitoneal tumors weighed. Antiangiogenic evaluated CD31 immunostaining alginate-encapsulate tumor assay. Detection proliferative cells apoptotic tissues performed Ki-67 staining TUNEL Stable expression detected groups. combination complexes exhibited enhanced activity, compared monotherapy alone (P<0.01). therapy exerted significant activity through antiangiogenesis, induction apoptosis suppression proliferation. Collectively, these observations provide evidence HPEI may have promising application human

参考文章(40)
R.F. Ozols, Progress in ovarian cancer European Journal of Cancer Supplements. ,vol. 1, pp. 43- 55 ,(2003) , 10.1016/S1359-6349(03)00008-9
Zhao X, Wen Yj, Wang L, Chen Xc, He X, Lin Xj, Wei Yq, Kan B, Dynamic progression of an intraperitoneal xenograft model of human ovarian cancer and its potential for preclinical trials. Journal of Experimental & Clinical Cancer Research. ,vol. 26, pp. 467- 474 ,(2007)
Erica M. Selva, Norbert Perrimon, Role of heparan sulfate proteoglycans in cell signaling and cancer Advances in Cancer Research. ,vol. 83, pp. 67- 80 ,(2001) , 10.1016/S0065-230X(01)83003-7
D. Ferber, GENE THERAPY: Safer and Virus-Free? Science. ,vol. 294, pp. 1638- 1642 ,(2001) , 10.1126/SCIENCE.294.5547.1638
Peter Carmeliet, Rakesh K. Jain, Angiogenesis in cancer and other diseases Nature. ,vol. 407, pp. 249- 257 ,(2000) , 10.1038/35025220
Viji Shridhar, Steve Kovats, Julie Staub, Ami Sen, John Lee, Jeremy Chien, Rajeswari Avula, Jim Lillie, David I. Smith, Identification of underexpressed genes in early- and late-stage primary ovarian tumors by suppression subtraction hybridization Cancer Research. ,vol. 62, pp. 262- 270 ,(2002)
Seth M. Cohen, Stephen J. Lippard, Cisplatin: from DNA damage to cancer chemotherapy. Progress in Nucleic Acid Research and Molecular Biology. ,vol. 67, pp. 93- 130 ,(2001) , 10.1016/S0079-6603(01)67026-0
Michael Schirner, Andreas Menrad, Martin R. Schneider, Jens Hoffmann, A Highly Sensitive Model for Quantification of in Vivo Tumor Angiogenesis Induced by Alginate-encapsulated Tumor Cells Cancer Research. ,vol. 57, pp. 3847- 3851 ,(1997)
Michael A. Gosselin, Wenjin Guo, Robert J. Lee, Efficient gene transfer using reversibly cross-linked low molecular weight polyethylenimine. Bioconjugate Chemistry. ,vol. 12, pp. 989- 994 ,(2001) , 10.1021/BC0100455