Anti-Angiogenic Gene Therapy of Prostate Cancer with Lentiviral Vectors.

摘要

Tumor progression induces the growth of endothelial cells by releasing angiogenic factors. This is accompanied by down-regulation of local tissue inhibitors of endothelian cell proliferation such as angiostatin and endostatin. Both proteins target normal endothelial cells and effectively regress large tumors in animals. However, animal studies demonstrate that an effective treatment requires long-term administration of angiogenesis inhibitors. Thus, delivery of angiogenesis inhibitor genes to tumor sites should increase local concentration of these proteins, leading to the retardation of tumor progression and metastasis. During this finding period, we have established stable human prostate cancer cell lines derived from PC3 cells transduced with HIV7/endo, HIV7/angio or both together. Expression of the angiogenesis inhibitors did not affect the proliferation of PC3 cells significantly. These PC cell lines produced and secreted sufficient amounts of angiogenesis inhibitors to inhibit the proliferation of primary human primary human umbilical vein endothelial cells (HUVEC) in culture. Subcutaneous implantation of these cells onto nude mice demonstrates that both proteins exert an effect on the ability of PC3 cells to form tumor in vivo.