Antitumor effects and radiosensitization of cytosine deaminase and thymidine kinase fusion suicide gene on colorectal carcinoma cells.
OBJECTIVE
To investigate the killing effect and radiosensitization of double suicide gene mediated by adenovirus on colorectal carcinoma cells.


METHODS
Colorectal carcinoma cell line SW480 was transfected with adenovirus expression vector containing cytosine deaminase (CD) and thymidine kinase (TK) fusion gene. The expression of CD-TK fusion gene was detected by reverse transcriptase-polymerase chain reaction. The toxic effect of ganciclovir (GCV) and 5-fluorocytosine (5-FC) on infected cells was determined by MTT assay. The radiosensitization of double suicide gene was evaluated by clonogenic assay.


RESULTS
After prodrugs were used, the survival rate of colorectal carcinoma cells was markedly decreased. When GCV and 5-FC were used in combination, the cytotoxicity and bystander effect were markedly superior to a single prodrug (chi2 = 30.371, P<0.01). Both GCV and 5-FC could sensitize colorectal carcinoma cells to the toxic effect of radiation, and greater radiosensitization was achieved when both prodrug were used in combination.


CONCLUSIONS
CD-TK double suicide gene can kill and radiosensitize colorectal carcinoma cells.
Wu
De-Hua
DH
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China. wudh@fimmu.com
Liu
Li
L
Chen
Long-Hua
LH
D000256:Adenoviridae / Q000235:genetics; D019677:Artificial Gene Fusion; D015179:Colorectal Neoplasms / Q000628:therapy*; D043525:Cytosine Deaminase / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D011355:Prodrugs / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D013937:Thymidine Kinase / Q000235:genetics*; D014407:Tumor Cells, Cultured
D011355:Prodrugs; D011838:Radiation-Sensitizing Agents; D013937:Thymidine Kinase; D043525:Cytosine Deaminase