The herpes simplex virus thymidine kinase/ganciclovir (HSV TK/GCV) system is one of\nthe best studied cancer suicide gene therapy systems. Our previous study showed that caspase 3\nexpression was upregulated and bladder tumor growth was significantly reduced in rats treated\nwith a combination of Bifidobacterium (BF) and HSV TK/GCV (BF-rTK/GCV). However, it was raised\nwhether the BF-mediated recombinant thymidine kinase combined with ganciclovir (BF-rTK/GCV)\nwas safe to administer via venous for cancer gene therapy. To answer this question, the antitumor\neffects of BF-rTK/GCV were mainly evaluated in a xenograft nude mouse model bearing MKN-45\ngastric tumor cells. The immune response, including analysis of cytokine profiles, was analyzed to\nevaluate the safety of intramuscular and intravenous injection of BF-rTK in BALB/c mice. The results\nsuggested that gastric tumor growth was significantly inhibited in vivo by BF-rTK/GCV. However,\nthe BF-rTK/GCV had no effect on mouse body weight, indicating that the treatment was safe for\nthe host. The results of cytokine profile analysis indicated that intravenous injection of a low dose\nof BF-rTK resulted in a weaker cytokine response than that obtained with intramuscular injection.\nFurthermore, immunohistochemical analysis showed that intravenous administration did not affect\nthe expression of immune-associated TLR2 and TLR4. Finally, the BF-rTK/GCV inhibited vascular\nendothelial growth factor (VEGF) expression in mouse model, which is helpful for inhibiting of tumor\nangiogenesis. That meant intravenous administration of BF-rTK/GCV was an effective and safe way\nfor cancer gene therapy.
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