Giermasz A, Grzela T, Nowis D, Makowski M, Czajka A, Stoklosa T, Lasek W, Dabrowsk A, Wiznerowicz M, Mackiewicz A, Jakóbisiak M
Department of Immunology, Centre for Biostructure Research, The Medical University of Warsaw, Poland.
Anticancer Res. 2001 Nov-Dec;21(6A):4001-4.
Butyric acid (NaBut) and its derivatives are well-known agents eliciting tumor cell differentiation and apoptosis. In experimental models, NaBut is also used to enhance the efficacy of viral vectors. With the use of B78 murine melanoma cells transduced with the retroviral vector containing human tumor necrosis factor alpha (hTNF-alpha) gene, we investigated the ability of NaBut to increase the cytokine expression. We observed an increase in hTNF-alpha expression in vitro after incubation with NaBut. We also describe that the NaBut pro-drug tributyrin is able to increase hTNF-alpha expression in transduced B78 cells in a tumor vaccination model in mice. This observation strongly suggests a novel potential role for NaBut and its derivatives in tumor therapy. It could be used not only as a therapeutic directly acting on tumor cells but, in parallel, as a genetic vaccine "enhancer".
丁酸(丁酸钠)及其衍生物是引发肿瘤细胞分化和凋亡的知名药物。在实验模型中,丁酸钠还被用于增强病毒载体的功效。通过使用用含人肿瘤坏死因子α(hTNF-α)基因的逆转录病毒载体转导的B78小鼠黑色素瘤细胞,我们研究了丁酸钠增加细胞因子表达的能力。我们观察到在与丁酸钠孵育后,体外hTNF-α表达增加。我们还描述了丁酸钠前体药物三丁酸甘油酯在小鼠肿瘤疫苗接种模型中能够增加转导的B78细胞中hTNF-α的表达。这一观察结果强烈表明丁酸钠及其衍生物在肿瘤治疗中具有新的潜在作用。它不仅可以用作直接作用于肿瘤细胞的治疗药物,而且同时还可以用作基因疫苗“增强剂”。