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Induction of sensitivity to ganciclovir in human hepatocellular carcinoma cells by adenovirus‐mediated gene transfer of herpes simplex virus thymidine kinase
Author(s) -
Qian Cheng,
Bilbao Roberto,
Bruña Oscar,
Prieto Jesús
Publication year - 1995
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840220119
Subject(s) - ganciclovir , thymidine kinase , herpes simplex virus , virology , gene transfer , hepatocellular carcinoma , thymidine , virus , cancer research , medicine , gene , biology , in vitro , human cytomegalovirus , genetics
We have analyzed the ability of a recombinant replication‐defective adenovirus to transfer the thymidine kinase gene of herpes simplex virus (HSV‐tk) into hepatocellular carcinoma (HCC) cells to confer sensitivity to ganciclovir. Three HCC cell lines (Hep3B, PLC/PRF/5, and HepG2) were efficiently infected in vitro by a recombinant adenovirus carrying lacZ reporter gene (Ad‐CMVlacZ). Expression of HSV‐tk in HCC cells infected with a recombinant adenovirus carrying HSV‐tk gene (AdCMVtk) induced sensitivity to ganciclovir in a dosedependent manner. A bystander killing effect was observed when 90% of uninfected tumor cells were mixed with only 10% of AdCMVtk‐infected cells. These data show that recombinant adenoviruses are efficient vectors for transduction of drug‐sensitizing genes to HCC cells in vitro . We suggest that a gene therapy approach to hepatocellular carcinoma can be established using adenoviral transfer of HSV‐tk to tumor cells and subsequent administration of ganciclovir. (H EPATOLOGY 1995; 22:118‐123.)