title: Efficient inhibition of an intraperitoneal xenograft model of human             ovarian cancer by HSulf-1 gene delivered by biodegradable cationic heparin-polyethyleneimine             nanogels.
abstract: The HSulf-1 (heparan sulfate 6-O-endosulfatase 1) gene is an important element             that modulates the sulfation status of heparan sulfate proteoglycans (HSPGs),             leading to the interference of HSPG-related signal transduction pathways. HSulf-1             plays a key role in regulating cell proliferation, tumorigenesis and angiogenesis.             Recently, some studies have reported that HSulf-1 is a down-regulated gene in             the majority of examined tumor types. In our present study, a recombinant plasmid             DNA carrying HSulf-1-cDNA (pHSulf-1) was constructed. The antitumor effect of             pHSulf-1 delivered by heparin-polyethyleneimine (HPEI) nanogels on human ovarian             cancer and the possible mechanisms of the antitumor efficacy in vivo were further             investigated. Heparin-polyethyleneimine (HPEI) nanogels, as a new safe non-viral             gene delivery carrier, were prepared to deliver the plasmid expressing HSulf-1             into HSulf-1-deficient SKOV3 human ovarian cancer cells in vitro and in vivo.             pHSulf-1 could be efficiently transfected into SKOV3 ovarian cancer cells by HPEI             nanogels in vitro and in vivo. Stable expression of HSulf-1 in vitro and in vivo             was verified by reverse transcription polymerase chain reaction (RT-PCR) and Western             blot analysis. Furthermore, a SKOV3 intraperitoneal ovarian carcinomatosis model             was established to investigate the growth inhibition function of pHSulf-1 in nude             mice. Tumor weight was measured. An anti-angiogenesis effect of pHSulf-1 in vivo             was detected by CD31 immunostaining and alginate-encapsulate tumor cell assay.             Assessment of apoptotic cells and proliferation index in tumor tissues were performed             by TUNEL assay and Ki‑67 immunostaining. Intraperitoneal injection of pHSulf-1/HPEI             complexes efficiently reduced tumor weight by approximately 87% compared with             control groups (P<0.01). Meanwhile, reduction in angiogenesis, inhibition of             cell proliferation, as well as induction of tumor cell apoptosis were observed,             without apparent systemic toxic effects. Collectively, these observations provide             the first evidence that pHSulf-1 delivered by HPEI nanogels may become a promising             therapeutic strategy against human ovarian cancer.
authors.affiliation: Department of Gynecology and Obstetrics, Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Maling
authors.initials: M
authors.lastname: Gou
authors.forename: Tao
authors.initials: T
authors.lastname: Yi
authors.forename: Chuan
authors.initials: C
authors.lastname: Xie
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Qi
authors.forename: Shengtao
authors.initials: S
authors.lastname: Zhou
authors.forename: Hongxin
authors.initials: H
authors.lastname: Deng
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001835:Body Weight; D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000080385:Nanogels; D009361:Neoplasm Invasiveness / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000628:therapy; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000633:toxicity; D011094:Polyethyleneimine / Q000737:chemistry* / Q000633:toxicity; D015238:Sulfotransferases / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D002412:Cations; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D006493:Heparin; C470791:SULF1 protein, human; D015238:Sulfotransferases