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

Abstract

Currently, great interest is focused on the anti-neoplastic effects of CXC chemokine ligand 10 (IP-10/CXCL10). IP-10 has shown significant antitumor and anti-metastatic properties via immunological, antiangiogenic and anti-neoplastic mechanisms. However, very few studies on the antitumor activity of IP-10 in human ovarian cancer have been reported. The use of polymeric nanoparticles to deliver functional genes intraperitoneally holds much promise as an effective therapy for ovarian cancer. In our study, a recombinant plasmid expressing IP-10 (pVITRO-IP-10) was constructed, and biodegradable cationic heparin-polyethyleneimine (HPEI) nanogels were prepared to deliver pVITRO-IP-10 into SKOV3 human ovarian cancer cells. Transfection efficiency 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 examined by Hoechst33258/PI staining and flow cytometry assays. The effect on the inhibition of angiogenesis was evaluated by tube formation assay using human umbilical vein endothelial cells (HUVECs). Moreover, a SKOV3 intraperitoneal ovarian carcinomatosis model was established to investigate the antitumor activity of HPEI+pVITRO-IP-10 complexes in nude mice. Tumor weights were evaluated during the treatment course. Cell proliferation and apoptosis were evaluated by Ki-67 immunochemical staining and TUNEL assay, and the antiangiogenic effect of pVITRO-IP-10 was assessed by CD31 immunochemical staining and alginate-encapsulated tumor cell assay. pVITRO-IP-10 was efficiently transfected into SKOV3 cells by HPEI nanogels. Intraperitoneal administration of HPEI+pVITRO-IP-10 complexes led to effective growth inhibition of ovarian cancer, in which tumor weight decreased by ~69.92% in the treatment group compared with that in the empty vector control group. Meanwhile, decreased cell proliferation, increased tumor cell apoptosis and reduction in angiogenesis were observed in the HPEI+pVITRO-IP-10 group compared with those in the control groups. These results indicated that HPEI nanogel delivery of pVITRO-IP-10 may be of value in the treatment against human ovarian cancer.

• Authors: Fan Yang, Malin Gou, Hongxin Deng, Tao Yi, Qian Zhong, Yuquan Wei, Xia Zhao
• Journal: Oncology reports (Oncol Rep) Vol. 28 Issue 2 Pg. 668-76 (Aug 2012) ISSN: 1791-2431 [Electronic] Greece
• PMID: 22684947 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CXCL10 protein, human
• Chemokine CXCL10
• Nanogels
• polyethylene glycol polyethyleneimine nanogel
• Polyethylene Glycols
• Polyethyleneimine
• Heparin

Topics

• Animals
• Apoptosis (genetics)
• Cell Growth Processes (genetics)
• Cell Line, Tumor
• Chemokine CXCL10 (biosynthesis, genetics)
• Cystadenocarcinoma, Serous (blood supply, genetics, pathology, therapy)
• Female
• Genetic Therapy (methods)
• Heparin (administration & dosage, chemistry)
• Human Umbilical Vein Endothelial Cells (cytology)
• Humans
• In Situ Nick-End Labeling
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nanogels
• Neovascularization, Pathologic (genetics, pathology, therapy)
• Ovarian Neoplasms (blood supply, genetics, pathology, therapy)
• Plasmids (administration & dosage, genetics)
• Polyethylene Glycols (administration & dosage, chemistry)
• Polyethyleneimine (administration & dosage, chemistry)
• Transfection (methods)
• Xenograft Model Antitumor Assays