Tumor-specific chemo-radio-gene therapy for colorectal cancer cells using adenovirus vector expressing the cytosine deaminase gene.
We studied the effect of suicide gene therapy using an adenovirus vector expressing the cytosine deaminase (CD) gene combined with irradiation therapy (chemo-radio-gene therapy) for human colorectal cancer cells. Since serum CEA levels are elevated in patients with some malignant tumors including colorectal cancer, we applied the CEA promoter to chemo-radio-gene therapy, expecting tumor-specific expression of the CD gene. In in vitro study, we succeeded in selective expression of the target CD gene and growth inhibition in only CEA-producing tumor cells; Further the inhibitory effect was enhanced by combination with radiation therapy in an irradiation dose-dependent manner. In addition, in in vivo study, a significant growth inhibition was observed in chemo-radio-gene therapy in comparison with radiation therapy alone or suicide gene therapy alone. Thus, we suggest that tumor-specific chemo-radio-gene therapy may be a useful strategy for human colorectal cancer.
Ueno
M
M
1st Department of Surgery, Nara Medical University, Kashihara, Japan. mu42724@naramed-u.ac.jp
Koyama
F
F
Yamada
Y
Y
Fujimoto
H
H
Takayama
T
T
Kamada
K
K
Naito
A
A
Hirao
S
S
Mukogawa
T
T
Hamada
H
H
Nakajima
Y
Y
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology*; D001711:Biotransformation; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy / Q000628:therapy*; D003131:Combined Modality Therapy; D043525:Cytosine Deaminase; D005437:Flucytosine / Q000493:pharmacokinetics / Q000494:pharmacology*; D005472:Fluorouracil / Q000493:pharmacokinetics / Q000494:pharmacology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009700:Nucleoside Deaminases / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000964:Antimetabolites, Antineoplastic; D002272:Carcinoembryonic Antigen; D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase; D005472:Fluorouracil