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

Yang,Fan; Gou,Malin; Deng,Hongxin; Yi,Tao; Zhong,Qian; Wei,Yuquan; Zhao,Xia

doi:10.3892/or.2012.1853

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

Authors:
- Fan Yang
- Malin Gou
- Hongxin Deng
- Tao Yi
- Qian Zhong
- Yuquan Wei
- Xia Zhao
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Affiliations: 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; State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, Chengdu 610041, Sichuan, P.R. China
Published online on: June 6, 2012 https://doi.org/10.3892/or.2012.1853
Pages: 668-676

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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.

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