Antitumor efficacy of cytosine deaminase-armed vaccinia virus plus 5-fluorocytosine in colorectal cancers
Antitumor efficacy of cytosine deaminase-armed vaccinia virus plus 5-fluorocytosine in colorectal cancers
复制标题
携带胞嘧啶脱氨酶的痘苗病毒加 5-氟胞嘧啶对结直肠癌的抗肿瘤功效
DOI：
10.1186/s12935-020-01340-6
复制
发表时间：
2020-06-15
影响因子：
5.8
通讯作者：
Zhou, Bin
中科院分区：
文献类型：
--
作者：
Ding, Yuedi;Fan, Jun;Zhou, Bin
BackgroundVaccinia viruses have emerged as attractive therapeutic candidates for cancer treatment due to their inherent ability of tumor tropism and oncolytic property. Cytosine deaminase (CD), which is derived from bacteria or yeast, can convert a relatively nontoxic prodrug 5-fluorocytosine (5-FC) into the active anticancer drug 5-Fluorouracil (5-FU). Vaccinia virus armed with the prodrug-activator CD gene would result in augmented antitumor effects that combined the effect of vaccinia virus and 5-FU together, and particularly limited the anticancer drug to tumor regions.MethodsThe attenuated vaccinia Tian Tan strain Guang 9 (VG9), with active yeast CD expression and thymidine kinase (TK) deficiency, was successfully constructed. Then, in vitro and in vivo antitumor efficacy of vaccinia VG9-CD plus 5-FC administration was evaluated in colorectal cancer cells.ResultsVaccinia viruses displayed different oncolytic potency in vitro cells, no relationship with whether they were cancer cells or normal cells. In colorectal tumor models, mice treated with vaccinia VG9-TK−showed better tumor remission ability and prolonged survival. Moreover, vaccinia VG9-CD in combination with gavage administration of 5-FC displayed the best antitumor efficacy, especially for the prolongation of survival.ConclusionsVaccinia VG9-CD in combination with 5-FC plays combined effect of vaccinia virus and chemotherapy, and becomes a promising virotherapy for cancer.
