Abstract
BackgroundInterferon-γ-inducible protein 10 (IP-10) is a potent inhibitor of tumor angiogenesis. It has been reported that the antiangiogenic therapy combined with chemotherapy has synergistic effects.MethodsTo elucidate the mechanisms of IP-10 gene combined with a chemotherapy agent, we intramuscularly injected pBLAST-IP-10 expression plasmid combined with gemcitabine into tumor-bearing mice.ResultsThe proliferation of endothelial cells was effectively inhibited by IP-10 combined with gemcitabine in vitro. Treatment with pBLAST-IP-10 twice a week for 4 weeks combined with gemcitabine 10 mg/kg (once a week) resulted in sustained high level of IP-10 protein in serum, inhibition of tumor growth and prolongation of the survival of tumor-bearing mice. Compared with administration of IP-10 plasmid or gemcitabine alone, the angiogenesis in tumors were apparently inhibited, and the numbers of apoptotic cells and lymphocytes in tumor increased in the combination therapy group.ConclusionOur data indicate that the gene therapy of antiangiogenesis by intramuscular delivery of plasmid DNA encoding IP-10 combined with gemcitabine has synergistic effects on tomor by inhibiting the proliferation of endothelail cells, inducing the apoptosis of tumor cells, and recruiting lymphocytes to tumor in murine models. The present findings provided evidence of antitumor effects of genetherapy combined with chemotherapy.
Highlights
Interferon-γ-inducible protein 10 (IP-10) is a potent inhibitor of tumor angiogenesis
Conditioned medium was obtained from COS cells transfected with empty plasmid, non-transfected cells and cells transfected with pBLAST-IP-10
Growing HUVEC, SVEC, NIH/3T3 were exposed to the conditioned medium from COS cells transfected with pBLAST-IP-10 for 72 h, or exposed to normal saline and gemcitabine
Summary
Interferon-γ-inducible protein 10 (IP-10) is a potent inhibitor of tumor angiogenesis. It has been reported that the antiangiogenic therapy combined with chemotherapy has synergistic effects. Angiogenesis, the formation of new blood vessels, is important for normal physiological processes, and for the development of pathologic conditions such as cancer, rheumatoid and inflammation. Accumulated evidences indicate that the growth and metastasis of solid tumors is dependent on angiogenesis. Journal of Experimental & Clinical Cancer Research 2008, 27:63 http://www.jeccr.com/content/27/1/63 phase of tumor growth. It has been reported that cytotoxic agents can impair neovasculature directly or indirectly [3]. Proliferative endothelial cells in new vessels are sensitive to cytotoxic agents [4]. Combination therapy, consisting of low-dose chemotherapy and antiangiogenesis, may produce improved efficacy and reduced toxicity due to the synergistic effect on tumors [4,5]
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