Herpes simplex virus thymidine kinase and ganciclovir suicide gene therapy for human pancreatic cancer.
OBJECTIVE
To investigate the in vitro effects of suicide gene therapy system of herpes simplex virus thymidine kinase gene (HSV-TK) in combination with the treatment of nucleotide analog-ganciclovir (GCV) on human pancreatic cancer, and to provide a novel clinical therapeutic method for human pancreatic cancer.


METHODS
We used a replication defective recombinant retrovirus vector GINaTK (bearing HSV-TK gene) to make packaging cell PA317 produce progeny virions. We then transferred the HSV-TK gene to target cells SW1990 using these progeny virions, and treated these gene-modified tumor cells with GCV to study the sensitivity of the cells to GCV and their bystander effects by routine MTT-method.


RESULTS
Packaging cell PA317/TK was successfully constructed, and we acquired SW1990/TK through virus progeny infection. These gene-modified pancreatic cancer cells were sensitive to the treatment of GCV compared with unmodified tumor cells (t=4.15, n=10, P<0.0025). We also observed a remarkable bystander effect by mixing two kinds of cells at different ratio.


CONCLUSIONS
Our data demonstrate that HSV-TK/GCV suicide gene therapy system is effective for treating experimental human pancreatic cancer, which is largely resistant to the common therapies, so the suicide gene therapy system may be a potential treatment approach for pancreatic cancer.
Wang
Jing
J
Genetics Research Center, School of Basic-Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China. wjing18@sohu.com
Lu
Xiao-Xuan
XX
Chen
Dao-Zhen
DZ
Li
Shu-Feng
SF
Zhang
Li-Shan
LS
D016475:3T3 Cells; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D015774:Ganciclovir / Q000627:therapeutic use*; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D010190:Pancreatic Neoplasms / Q000628:therapy*; D018139:Simplexvirus / Q000201:enzymology*; D013937:Thymidine Kinase / Q000235:genetics*
D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir