Unidad de Transferencia Genética, Instituto de Oncología "Ángel H. Roffo", Universidad de Buenos Aires, Buenos Aires, Argentina.
Vet Comp Oncol. 2022 Jun;20(2):372-380. doi: 10.1111/vco.12780. Epub 2021 Nov 17.
We tested the efficacy of a yeast cytosine deaminase::uracil phosphoribosyl transferase/5-fluorocytosine (CDU/5-FC) non-viral suicide system on eight established canine melanoma cell lines. Albeit with different degree of sensitivity 5 days after lipofection, this system was significantly efficient killing melanoma cells, being four cell lines highly, two fairly and two not very sensitive to CDU/5-FC (their respective IC ranging from 0.20 to 800 μM 5-FC). Considering the relatively low lipofection efficiencies, a very strong bystander effect was verified in the eight cell lines: depending on the cell line, this effect accounted for most of the induced cell death (from 70% to 95%). In our assay conditions, we did not find useful interactions either with the herpes simplex thymidine kinase/ganciclovir suicide system (in sequential or simultaneous modality) or with cisplatin and bleomycin chemotherapeutic drugs. Furthermore, only two cell lines displayed limited useful interactions of the CDU/5-FC either with interferon-β gene transfer or the proteasome inhibitor bortezomib respectively. These results would preclude a wide use of these combinations. However, the fact that all the tested cells were significantly sensitive to the CDU/5-FC system encourages further research as a gene therapy tool for local control of canine melanoma.
:尿嘧啶磷酸核糖转移酶/5-氟胞嘧啶（CDU/5-FC）非病毒自杀系统在 8 株建立的犬黑色素瘤细胞系中的疗效。尽管在脂质体转染后 5 天的敏感性不同，但该系统对黑色素瘤细胞的杀伤效率显著，其中 4 株细胞高度敏感，2 株中度敏感，2 株不太敏感（其各自的 IC50 范围从 0.20 到 800 μM 5-FC）。考虑到相对较低的脂质体转染效率，在 8 株细胞中证实了非常强的旁观者效应：根据细胞系的不同，该效应占诱导细胞死亡的大部分（70%至 95%）。在我们的检测条件下，我们没有发现与单纯疱疹胸苷激酶/更昔洛韦自杀系统（顺序或同时模式）或顺铂和博来霉素化疗药物的有用相互作用。此外，只有 2 株细胞系显示出 CDU/5-FC 与干扰素-β基因转移或蛋白酶体抑制剂硼替佐米的有限的有用相互作用。这些结果将排除这些组合的广泛应用。然而，所有测试的细胞对 CDU/5-FC 系统均显著敏感，这鼓励了进一步的研究，作为局部控制犬黑色素瘤的基因治疗工具。
