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Currently, great interest is focused on the anti-neoplastic effects of CXCchemokine ligand 10 (IP-10/CXCL10). IP-10 has shown significant antitumor andanti-metastatic properties via immunological, antiangiogenic and anti-neoplasticmechanisms. However, very few studies on the antitumor activity of IP-10 in humanovarian cancer have been reported. The use of polymeric nanoparticles to deliverfunctional genes intraperitoneally holds much promise as an effective therapyfor ovarian cancer. In our study, a recombinant plasmid expressing IP-10 (pVITRO-IP-10)was constructed, and biodegradable cationic heparin-polyethyleneimine (HPEI) nanogelswere prepared to deliver pVITRO-IP-10 into SKOV3 human ovarian cancer cells. Transfectionefficiency was detected by expression profiling of green fluorescent protein.The expression of IP-10 was determined using RT-PCR and western blot analysis.In vitro, cell proliferation was evaluated by MTT assay. Apoptosis was examinedby Hoechst33258/PI staining and flow cytometry assays. The effect on the inhibitionof angiogenesis was evaluated by tube formation assay using human umbilical veinendothelial cells (HUVECs). Moreover, a SKOV3 intraperitoneal ovarian carcinomatosismodel was established to investigate the antitumor activity of HPEI+pVITRO-IP-10complexes in nude mice. Tumor weights were evaluated during the treatment course.Cell proliferation and apoptosis were evaluated by Ki-67 immunochemical stainingand TUNEL assay, and the antiangiogenic effect of pVITRO-IP-10 was assessed byCD31 immunochemical staining and alginate-encapsulated tumor cell assay. pVITRO-IP-10was efficiently transfected into SKOV3 cells by HPEI nanogels. Intraperitonealadministration of HPEI+pVITRO-IP-10 complexes led to effective growth inhibitionof ovarian cancer, in which tumor weight decreased by ~69.92% in the treatmentgroup compared with that in the empty vector control group. Meanwhile, decreasedcell proliferation, increased tumor cell apoptosis and reduction in angiogenesiswere observed in the HPEI+pVITRO-IP-10 group compared with those in the controlgroups. These results indicated that HPEI nanogel delivery of pVITRO-IP-10 maybe of value in the treatment against human ovarian cancer.

oncology reports

Efficient inhibition of ovarian cancer by recombinant CXC chemokine ligand 10 delivered by novel biodegradable cationic heparin-polyethyleneimine nanogels