Abstract
BackgroundThe use of adenoviral vector for gene therapy is still an important strategy for advanced cancers, however, the lack of the requisite coxsackie-adenovirus receptor in cancer cells and host immune response to adenovirus limit the application of adenoviral vector in vivo.MethodWe designed the antiangiogenic gene therapy with recombinant PEDF adenovirus (Ad-PEDF) encapsulated in cationic liposome (Ad-PEDF/Liposome), and investigated the anti-tumor efficacy of Ad-PEDF/Liposome complex on inhibition of tumor metastasis.ResultsWe found that systemic administration of Ad-PEDF/liposome was well tolerated and resulted in marked suppression of tumor growth, and was more potent than uncoated Ad-PEDF to induce apoptosis in B16-F10 melanoma cells and inhibit murine pulmonary metastases in vivo. After Ad-luciferase was encapsulated with liposome, its distribution decreased in liver and increased in lung. The anti-Ad IgG level of Ad-PEDF/Liposome was significantly lower than Ad-PEDF used alone.ConclusionThe present findings provide evidences of systematic administration of cationic liposome-encapsulated Ad-PEDF in pulmonary metastatic melanoma mice model, and show an encouraging therapeutic effect for further exploration and application of more complexes based on liposome-encapsulated adenovirus for more cancers.
Highlights
The use of adenoviral vector for gene therapy is still an important strategy for advanced cancers, the lack of the requisite coxsackie-adenovirus receptor in cancer cells and host immune response to adenovirus limit the application of adenoviral vector in vivo
We found that Adenoviral vector (Ad)-GFP encapsulated with DOTAP and cholesterol liposome shows increased transfection ability in B16-F10 melanoma cells
The expression of Pigment epithelium-derived factor (PEDF) transfected by the adenovirus carrying PEDF gene (Ad-PEDF)/ Liposome complexes was much higher than that of Recombined adenovirus carrying PEDF gene (AdPEDF) and there was noting in Ad-null infected cells
Summary
The use of adenoviral vector for gene therapy is still an important strategy for advanced cancers, the lack of the requisite coxsackie-adenovirus receptor in cancer cells and host immune response to adenovirus limit the application of adenoviral vector in vivo. Melanoma is a tumor of transformed melanocytes; and it is a potentially serious type of skin cancer [1], which is one of the most highly invasive and metastatic tumors. Malignant melanoma is an increasingly common malignancy, and its mortality rates have been rapidly increasing above those of any other cancer in recent years [2,3]. Melanoma can spread "silently" at an early stage without any symptoms of metastasis, and owing to the incidence of melanoma is increasing in last decades, the mortality rate of melanoma is still increasing [3]. It is imminent to Angiogenesis plays a critical role in the process of growth and metastasis of primary solid tumors [4,5]. The current review summarizes existing knowledge of the mechanisms of angiogenesis in melanoma [11], and current anti-angiogenic therapeutic strategies and their targets confirmed the effect of anti-angiogenic therapy on melanoma [12,13,14,15]
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