| Title | Antitumor efficacy of oncolytic HSV-1 expressing cytosine deaminase is synergistically enhanced by DPD down-regulation and EMT inhibition in uveal melanoma xenograft |
| Authors | Liu, Sisi Zhang, Junwen Fang, Sheng Su, Xiaodong Zhang, Qing Zhu, Guidong Zhu, Li Zhao, Mingwei Liu, Fusheng |
| Affiliation | Peking Univ, Beijing Key Lab Diag & Therapy Retinal & Choroid, Peoples Hosp,Coll Optometry, Eye Dis & Optometry Inst,Hlth Sci Ctr,Dept Ophtha, Beijing, Peoples R China Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Brain Tumor Res Ctr,Beijing Neurosurg Inst, Beijing, Peoples R China |
| Keywords | HERPES-SIMPLEX-VIRUS DIHYDROPYRIMIDINE DEHYDROGENASE THYMIDYLATE SYNTHASE THYMIDINE KINASE CELL-LINES CANCER ACTIVATION THERAPY 5-FLUOROCYTOSINE 5-FLUOROURACIL |
| Issue Date | 28-Dec-2020 |
| Publisher | CANCER LETTERS |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/599561 |
| ISSN | 0304-3835 |
| DOI | 10.1016/j.canlet.2020.09.013 |
| Indexed | SCI(E) |
| Appears in Collections: | 人民医院 |
