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Article

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
  • View Affiliations / Copyright

    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
  • Pages: 668-676
    |
    Published online on: June 6, 2012
       https://doi.org/10.3892/or.2012.1853
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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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Copy and paste a formatted citation
Spandidos Publications style
Yang F, Gou M, Deng H, Yi T, Zhong Q, Wei Y and Zhao X: Efficient inhibition of ovarian cancer by recombinant CXC chemokine ligand 10 delivered by novel biodegradable cationic heparin-polyethyleneimine nanogels. Oncol Rep 28: 668-676, 2012.
APA
Yang, F., Gou, M., Deng, H., Yi, T., Zhong, Q., Wei, Y., & Zhao, X. (2012). Efficient inhibition of ovarian cancer by recombinant CXC chemokine ligand 10 delivered by novel biodegradable cationic heparin-polyethyleneimine nanogels. Oncology Reports, 28, 668-676. https://doi.org/10.3892/or.2012.1853
MLA
Yang, F., Gou, M., Deng, H., Yi, T., Zhong, Q., Wei, Y., Zhao, X."Efficient inhibition of ovarian cancer by recombinant CXC chemokine ligand 10 delivered by novel biodegradable cationic heparin-polyethyleneimine nanogels". Oncology Reports 28.2 (2012): 668-676.
Chicago
Yang, F., Gou, M., Deng, H., Yi, T., Zhong, Q., Wei, Y., Zhao, X."Efficient inhibition of ovarian cancer by recombinant CXC chemokine ligand 10 delivered by novel biodegradable cationic heparin-polyethyleneimine nanogels". Oncology Reports 28, no. 2 (2012): 668-676. https://doi.org/10.3892/or.2012.1853
Copy and paste a formatted citation
x
Spandidos Publications style
Yang F, Gou M, Deng H, Yi T, Zhong Q, Wei Y and Zhao X: Efficient inhibition of ovarian cancer by recombinant CXC chemokine ligand 10 delivered by novel biodegradable cationic heparin-polyethyleneimine nanogels. Oncol Rep 28: 668-676, 2012.
APA
Yang, F., Gou, M., Deng, H., Yi, T., Zhong, Q., Wei, Y., & Zhao, X. (2012). Efficient inhibition of ovarian cancer by recombinant CXC chemokine ligand 10 delivered by novel biodegradable cationic heparin-polyethyleneimine nanogels. Oncology Reports, 28, 668-676. https://doi.org/10.3892/or.2012.1853
MLA
Yang, F., Gou, M., Deng, H., Yi, T., Zhong, Q., Wei, Y., Zhao, X."Efficient inhibition of ovarian cancer by recombinant CXC chemokine ligand 10 delivered by novel biodegradable cationic heparin-polyethyleneimine nanogels". Oncology Reports 28.2 (2012): 668-676.
Chicago
Yang, F., Gou, M., Deng, H., Yi, T., Zhong, Q., Wei, Y., Zhao, X."Efficient inhibition of ovarian cancer by recombinant CXC chemokine ligand 10 delivered by novel biodegradable cationic heparin-polyethyleneimine nanogels". Oncology Reports 28, no. 2 (2012): 668-676. https://doi.org/10.3892/or.2012.1853
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