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The HSulf-1 (heparan sulfate 6-O-endosulfatase 1) gene is an important elementthat modulates the sulfation status of heparan sulfate proteoglycans (HSPGs),leading to the interference of HSPG-related signal transduction pathways. HSulf-1plays a key role in regulating cell proliferation, tumorigenesis and angiogenesis.Recently, some studies have reported that HSulf-1 is a down-regulated gene inthe majority of examined tumor types. In our present study, a recombinant plasmidDNA carrying HSulf-1-cDNA (pHSulf-1) was constructed. The antitumor effect ofpHSulf-1 delivered by heparin-polyethyleneimine (HPEI) nanogels on human ovariancancer and the possible mechanisms of the antitumor efficacy in vivo were furtherinvestigated. Heparin-polyethyleneimine (HPEI) nanogels, as a new safe non-viralgene delivery carrier, were prepared to deliver the plasmid expressing HSulf-1into 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 HPEInanogels in vitro and in vivo. Stable expression of HSulf-1 in vitro and in vivowas verified by reverse transcription polymerase chain reaction (RT-PCR) and Westernblot analysis. Furthermore, a SKOV3 intraperitoneal ovarian carcinomatosis modelwas established to investigate the growth inhibition function of pHSulf-1 in nudemice. Tumor weight was measured. An anti-angiogenesis effect of pHSulf-1 in vivowas detected by CD31 immunostaining and alginate-encapsulate tumor cell assay.Assessment of apoptotic cells and proliferation index in tumor tissues were performedby TUNEL assay and Ki‑67 immunostaining. Intraperitoneal injection of pHSulf-1/HPEIcomplexes efficiently reduced tumor weight by approximately 87% compared withcontrol groups (P&lt;0.01). Meanwhile, reduction in angiogenesis, inhibition ofcell proliferation, as well as induction of tumor cell apoptosis were observed,without apparent systemic toxic effects. Collectively, these observations providethe first evidence that pHSulf-1 delivered by HPEI nanogels may become a promisingtherapeutic strategy against human ovarian cancer.

oncology reports

Efficient inhibition of an intraperitoneal xenograft model of human ovarian cancer by HSulf-1 gene delivered by biodegradable cationic heparin-polyethyleneimine nanogels