Herpes simplex virus thymidine kinase and ganciclovir suicide gene therapy for human pancreatic cancer

World J Gastroenterol. 2004 Feb 1;10(3):400-3. doi: 10.3748/wjg.v10.i3.400.


Aim: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Antiviral Agents / therapeutic use*
  • Cell Line, Tumor
  • Ganciclovir / therapeutic use*
  • Genes, Transgenic, Suicide*
  • Genetic Therapy*
  • Humans
  • Mice
  • Pancreatic Neoplasms / therapy*
  • Simplexvirus / enzymology*
  • Thymidine Kinase / genetics*


  • Antiviral Agents
  • Thymidine Kinase
  • Ganciclovir