Synthetic radiation-inducible promoters mediated HSV-TK/GCV gene therapy in the treatment of oral squamous cell carcinoma.
OBJECTIVE
To investigate the therapeutic effect of herpes simplex virus thymidine kinase (HSV-TK) gene mediated by synthetic radiation-inducible promoters in the treatment of oral squamous cell carcinoma (OSCC) in vitro and in vivo.


METHODS
The plasmids pcDNA3.1(+)E6-HSV-TK were constructed, in which the HSV-TK genes were mediated by synthetic radiation-inducible promoters. The recombined plasmids were transfected into the Tca8113 cells and golden hamster buccal carcinoma, respectively. Low-dose radiotherapy was used to upregulate the HSV-TK genes expression. HSV-TK mRNA was assayed by RT-PCR. Apoptosis and proliferating cell nuclear antigen were detected respectively by in situ end-labeling and immunohistochemical method.


RESULTS
Compared with control group, the comparative survival rate of Tca8113 cells in HSV-TK/GCV/IR group was markedly decreased and the golden hamster buccal carcinoma in HSV-TK/GCV/IR group was obviously suppressed. Up-regulation of HSV-TK gene expression was found in the Tca8113 cells and in the golden hamster buccal carcinoma resulting from exposure to low-dose irradiation. The apoptosis indexes in Tca8113 cells or golden hamster buccal carcinoma with irradiation were markedly higher than those without irradiation. At the same time, the proliferation indexes in Tca8113 cells or golden hamster buccal carcinoma with irradiation were markedly lower than those without irradiation.


CONCLUSIONS
The results indicate that the synthetic radiation-inducible promoters can serve as a molecular switch to adjust the expression of HSV-TK gene in the treatment of OSCC, and low-dose induction radiation can significantly improve therapeutic efficiency.
Yu
D-S
DS
Institute of Stomatological Research, Sun Yat-sen University, Guangzhou, Guangdong, China.
Zhao
W
W
Huang
H-Z
HZ
Hu
X-W
XW
Liu
X-Q
XQ
Tang
H-K
HK
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D006224:Cricetinae; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000528:radiation effects; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D009062:Mouth Neoplasms / Q000473:pathology / Q000628:therapy*; D010957:Plasmids / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000528:radiation effects; D011829:Radiation Dosage; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics / Q000627:therapeutic use*; D014162:Transfection / Q000379:methods; D015854:Up-Regulation / Q000528:radiation effects
D018809:Proliferating Cell Nuclear Antigen; D013937:Thymidine Kinase