Antitumor efficacy of cytosine deaminase-armed vaccinia virus plus 5-fluorocytosine in colorectal cancers
Abstract Background Vaccinia 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-fluorocytos...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-06-01
|
| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12935-020-01340-6 |
| _version_ | 1818064167633944576 |
|---|---|
| author | Yuedi Ding Jun Fan Lili Deng Biao Huang Bin Zhou |
| author_facet | Yuedi Ding Jun Fan Lili Deng Biao Huang Bin Zhou |
| author_sort | Yuedi Ding |
| collection | DOAJ |
| description | Abstract Background Vaccinia 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. Methods The 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. Results Vaccinia 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. Conclusions Vaccinia VG9-CD in combination with 5-FC plays combined effect of vaccinia virus and chemotherapy, and becomes a promising virotherapy for cancer. |
| first_indexed | 2024-12-10T14:31:42Z |
| format | Article |
| id | doaj.art-8d930a159c1e44be800beef0d8eebfe9 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-10T14:31:42Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-8d930a159c1e44be800beef0d8eebfe92022-12-22T01:44:54ZengBMCCancer Cell International1475-28672020-06-0120111210.1186/s12935-020-01340-6Antitumor efficacy of cytosine deaminase-armed vaccinia virus plus 5-fluorocytosine in colorectal cancersYuedi Ding0Jun Fan1Lili Deng2Biao Huang3Bin Zhou4NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear MedicineNHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear MedicineNHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear MedicineNHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear MedicineNHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear MedicineAbstract Background Vaccinia 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. Methods The 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. Results Vaccinia 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. Conclusions Vaccinia VG9-CD in combination with 5-FC plays combined effect of vaccinia virus and chemotherapy, and becomes a promising virotherapy for cancer.http://link.springer.com/article/10.1186/s12935-020-01340-6Vaccinia virusCytosine deaminaseAntitumor efficacyColorectal cancer |
| spellingShingle | Yuedi Ding Jun Fan Lili Deng Biao Huang Bin Zhou Antitumor efficacy of cytosine deaminase-armed vaccinia virus plus 5-fluorocytosine in colorectal cancers Cancer Cell International Vaccinia virus Cytosine deaminase Antitumor efficacy Colorectal cancer |
| title | Antitumor efficacy of cytosine deaminase-armed vaccinia virus plus 5-fluorocytosine in colorectal cancers |
| title_full | Antitumor efficacy of cytosine deaminase-armed vaccinia virus plus 5-fluorocytosine in colorectal cancers |
| title_fullStr | Antitumor efficacy of cytosine deaminase-armed vaccinia virus plus 5-fluorocytosine in colorectal cancers |
| title_full_unstemmed | Antitumor efficacy of cytosine deaminase-armed vaccinia virus plus 5-fluorocytosine in colorectal cancers |
| title_short | Antitumor efficacy of cytosine deaminase-armed vaccinia virus plus 5-fluorocytosine in colorectal cancers |
| title_sort | antitumor efficacy of cytosine deaminase armed vaccinia virus plus 5 fluorocytosine in colorectal cancers |
| topic | Vaccinia virus Cytosine deaminase Antitumor efficacy Colorectal cancer |
| url | http://link.springer.com/article/10.1186/s12935-020-01340-6 |
| work_keys_str_mv | AT yuediding antitumorefficacyofcytosinedeaminasearmedvacciniavirusplus5fluorocytosineincolorectalcancers AT junfan antitumorefficacyofcytosinedeaminasearmedvacciniavirusplus5fluorocytosineincolorectalcancers AT lilideng antitumorefficacyofcytosinedeaminasearmedvacciniavirusplus5fluorocytosineincolorectalcancers AT biaohuang antitumorefficacyofcytosinedeaminasearmedvacciniavirusplus5fluorocytosineincolorectalcancers AT binzhou antitumorefficacyofcytosinedeaminasearmedvacciniavirusplus5fluorocytosineincolorectalcancers |