Differential efficacy of suicide gene therapy by herpes simplex virus-thymidine kinase gene reflects the status of p53 gene in human esophageal cancer cells.
We examined the effect of herpes simplex virus-thymidine kinase gene (HSV-TK)-mediated suicide gene therapy on human esophageal cancer. Two human lines, T.Tn cells which bears truncated p53 and TE2 cells with wild-type p53, were transduced with the HSV-TK gene and tested for their sensitivities to a prodrug, ganciclovir (GCV). The transduced cells, T.Tn/TK and TE2/TK, increased in vitro sensitivity to GCV compared with that of respective wild-type cells. However, the growth suppression of T.Tn/TK tumors induced by GCV was marginal in nude mice and the tumors regrew thereafter. In contrast, the growth of TE2/TK tumors was significantly inhibited by GCV and all the tumors disappeared. The status of the p53 gene of tumor cells thereby may influence the efficacy of the HSV-TK/GCV system.
Matsubara
H
H
Department of Surgery (II), School of Medicine, Chiba University, Japan.
Kawamura
K
K
Sugaya
M
M
Koide
Y
Y
Gunji
Y
Y
Takenaga
K
K
Asano
T
T
Ochiai
T
T
Sakiyama
S
S
Tagawa
M
M
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000628:therapy*; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology; D016158:Genes, p53 / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018139:Simplexvirus / Q000235:genetics*; D013937:Thymidine Kinase / Q000235:genetics*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir