Uveal melanoma (UM) is the most common intraocular tumor in adults and has a high incidence of metastases. Possible treatments remain limited in UM with enucleation and radiation, leading to poor prognosis in this chemo-resistant carcinoma. Thus, urging demand for novel treatment is needed. We examined the antitumor efficacy of a new recombinant oncolytic herpes simplex virus type 1 (oHSV-1) armed with E.coli cytosine deaminase (CD). We determined the efficacy of the oncolytic virus in UM cell lines. In vivo experiments showed that oHSV-CD/5-fluorocytosine (5-FC) treatment reduce tumor volume and prolonged survival. We further demonstrated the molecular mechanisms of oHSV-CD/5-FC treatment. The oncolytic virus down-regulated IL-6 expression and thereby reversed the epithelial-mesenchymal transition (EMT) phenotype. Dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme in 5-fluorouracil (5-FU) metabolism, was also down-regulated. Therefore, the efficacy of oHSV-CD/5-FC was synergistically enhanced by DPD down-regulation and EMT inhibition. This study provides solid evidence for the antitumor efficacy of oHSV-CD/5-FC treatment in vitro and in vivo. The molecular mechanisms of this treatment may bring a new therapeutic approach for future treatment of UM.

葡萄膜黑色素瘤（UM）是成人中最常见的眼内肿瘤，并且转移率很高。摘除术和放射治疗对UM的可能治疗仍然有限，导致这种化学耐药性癌症的预后不良。因此，迫切需要新颖的治疗方法。我们研究与武装新的重组溶瘤单纯疱疹病毒1型（oHSV-1）的抗肿瘤功效大肠杆菌胞嘧啶脱氨酶（CD）。我们确定了溶瘤病毒在UM细胞系中的功效。体内实验表明，oHSV-CD / 5-氟胞嘧啶（5-FC）治疗可减少肿瘤体积并延长生存期。我们进一步证明了oHSV-CD / 5-FC治疗的分子机制。溶瘤病毒下调IL-6表达，从而逆转上皮-间质转化（EMT）表型。二氢嘧啶脱氢酶（DPD），5-氟尿嘧啶（5-FU）代谢中的限速酶，也被下调。因此，通过DPD下调和EMT抑制可协同增强oHSV-CD / 5-FC的疗效。本研究为oHSV-CD / 5-FC治疗的抗肿瘤功效的确凿证据在体外和体内。这种治疗的分子机制可能为将来的UM治疗带来新的治疗方法。