In vitro model of suicide gene therapy for alpha-fetoprotein-producing gastric cancer.
BACKGROUND
Gastric adenocarcinoma producing alpha-fetoprotein (AFP) has a very poor prognosis. In search of new therapeutic strategies against AFP-producing gastric cancer, we examined the efficacy of suicide gene therapy, which has been effective on AFP-producing hepatoma.


METHODS
The herpes simplex virus thymidine kinase (HSVtk) gene was transduced into an AFP-producing gastric adenocarcinoma cell line, FU97, using adenovirus vectors carrying the constructed AFP enhancer/promoter element, followed by ganciclovir (GCV) administration.


RESULTS
Expression of the transgene was evident in FU97 but not in an AFP-nonproducing gastric adenocarcinoma cell line, MKN28, which meant that AFP enhancer/promoter-specific transcriptional targeting was achieved by the vectors. The viability of FU97 but not of MKN28 significantly decreased after the suicide gene therapy in vitro.


CONCLUSIONS
Therapeutic application of the AFP enhancer/promoter-specific transfer of the HSVtk gene followed by GCV administration against AFP-producing gastric cancer deserves attention and further research.
Nakaya
Hiroki
H
Departments of Pathology/Pathophysiology, Gastroenterology and Hematology, Division of Pathophysiological Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Ishizu
Akihiro
A
Ikeda
Hitoshi
H
Tahara
Masahiko
M
Shindo
Junri
J
Itoh
Ryoko
R
Takahashi
Toshiyuki
T
Asaka
Masahiro
M
Ishikura
Hiroshi
H
Yoshiki
Takashi
T
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics; D015774:Ganciclovir / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D011401:Promoter Regions, Genetic; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000096:biosynthesis* / Q000235:genetics*
D000509:alpha-Fetoproteins; D013937:Thymidine Kinase; D015774:Ganciclovir