Tumor-specific chemo-radio-gene therapy for colorectal cancer cells using adenovirus vector expressing the cytosine deaminase gene

M Ueno; F Koyama; Y Yamada; H Fujimoto; T Takayama; K Kamada; A Naito; S Hirao; T Mukogawa; H Hamada; Y Nakajima

Tumor-specific chemo-radio-gene therapy for colorectal cancer cells using adenovirus vector expressing the cytosine deaminase gene

Anticancer Res. 2001 Jul-Aug;21(4A):2601-8.

Authors

M Ueno¹, F Koyama, Y Yamada, H Fujimoto, T Takayama, K Kamada, A Naito, S Hirao, T Mukogawa, H Hamada, Y Nakajima

Affiliation

¹ 1st Department of Surgery, Nara Medical University, Kashihara, Japan. [email protected]

PMID: 11724328

Abstract

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.

MeSH terms

Adenocarcinoma / genetics
Adenocarcinoma / metabolism
Adenocarcinoma / radiotherapy
Adenocarcinoma / therapy*
Adenoviridae / genetics
Animals
Antimetabolites, Antineoplastic / pharmacokinetics
Antimetabolites, Antineoplastic / pharmacology*
Biotransformation
Carcinoembryonic Antigen / biosynthesis
Cell Division / drug effects
Cell Division / genetics
Cell Division / radiation effects
Colorectal Neoplasms / genetics
Colorectal Neoplasms / metabolism
Colorectal Neoplasms / radiotherapy
Colorectal Neoplasms / therapy*
Combined Modality Therapy
Cytosine Deaminase
Flucytosine / pharmacokinetics
Flucytosine / pharmacology*
Fluorouracil / pharmacokinetics
Fluorouracil / pharmacology
Genetic Therapy / methods*
Genetic Vectors / genetics
HT29 Cells
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Nucleoside Deaminases / genetics*
Nucleoside Deaminases / metabolism
Tumor Cells, Cultured
Xenograft Model Antitumor Assays

Substances

Antimetabolites, Antineoplastic
Carcinoembryonic Antigen
Flucytosine
Nucleoside Deaminases
Cytosine Deaminase
Fluorouracil