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Antitumor effect of chondroitin sulfate‐coated ternary granulocyte macrophage‐colony‐stimulating factor plasmid complex for ovarian cancer
Author(s) -
Hamada Katsuyuki,
Yoshihara Chieko,
Ito Tomoko,
Tani Kenzaburo,
Tagawa Masatoshi,
Sakuragawa Norio,
Itoh Hiroshi,
Koyama Yoshiyuki
Publication year - 2012
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1647
Subject(s) - chondroitin sulfate , hyaluronic acid , transfection , microbiology and biotechnology , chemistry , ovarian cancer , biochemistry , biology , cancer , medicine , glycosaminoglycan , gene , genetics
Abstract Background Although replication‐competent viruses have been developed for treating cancers, their cytotoxic effects are insufficient as a result of infection inhibited by the generation of neutralizing antibodies, and systemic administration is difficult as a result of the life‐threatening serious side‐effects of virus‐induced cytokine surge. To overcome these critical problems, we devised a plasmid/polycation/polyanion complex and assessed the potential of ternary plasmid complexes coated with chondroitin sulfate in gene therapy for ovarian cancer. The antitumor effects of chondroitin sulfate‐coated complex as an anionic component were compared with those of hyaluronic acid on ovarian cancer. Methods Plasmid harboring the gene of murine granulocyte macrophage‐colony‐stimulating factor (mGM‐CSF) was complexed with polyethyleneimine (PEI) and hyaluronic acid or chondroitin sulfate. Murine ovarian cancer cells were injected into (C57BL/6 × C3H/He) F 1 mice to prepare a subcutaneous or intraperitoneal tumor model. Results DNA/PEI was charged positively and DNA/PEI/chondroitin sulfate or DNA/PEI/hyaluronic acid was charged negatively. Plasmid‐green fluorescent protein (GFP)/PEI coated with 10‐kilodalton (kDa) chondroitin sulfate increased transfection efficiency compared to coating with chondroitin sulfate of higher‐molecular‐weight or hyaluronic acid. The transfection efficiency of GFP/PEI/10‐kDa chondroitin sulfate in ovarian cancer cells was six‐fold higher than that in normal cells. Intraperitoneal injection of mGM‐CSF/PEI coated with 10‐kDa chondroitin sulfate prolonged survival compared to that coated with hyaluronic acid. Intratumoral injection of mGM‐CSF/PEI coated with 10‐kDa chondroitin sulfate achieved mouse survival rates of 100%, although that with hyaluronic acid did not. Conclusions These findings suggest that GM‐CSF/PEI coated with 10‐kDa chondroitin sulfate has the potential for use in gene therapy of ovarian cancer. Copyright © 2012 John Wiley & Sons, Ltd.