Chemo-radio-gene therapy for colorectal cancer cells using Escherichia coli uracil phosphoribosyltransferase gene.
5-Fluorouracil (5-FU) is one of the most widely used chemotherapeutic agents, and is known to be a radiosensitizer. Previously, we reported that adenoviral transduction of the Escherichia coli (E. coli) uracil phosphoribosyltransferase (UPRT) gene induced marked sensitivity in human colon cancer cells to 5-FU. The aim of the current study was to investigate the efficacy of virally-directed UPRT and 5-FU to enhance the radiosensitivity of HT29 human colon cancer cells. Cytotoxicity as a result of radiation treatment following AdCA-UPRT infection and 5-FU exposure was confirmed by radiation dose-response analysis with colony formation assay. In vivo chemoradio-gene therapy using the UPRT/5-FU/radiation system showed tumor regressive effects even against large HT29-established subcutaneous tumors in nude mice. Our results suggested that adenovirus-mediated UPRT gene transduction combined with 5-FU administration and radiation may be an effective new chemo-radio-gene therapy for colorectal cancer.
Koyama
Fumikazu
F
First Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara-city, Nara 634-8522, Japan. fkoyama@naramed-u.ac.jp
Fujii
Hisao
H
Mukogawa
Tomohide
T
Ueno
Masato
M
Hamada
Hirofumi
H
Ishikawa
Hirofumi
H
Doi
Shinya
S
Nakao
Takeshi
T
Matsumoto
Hiroshi
H
Shimatani
Hidehiko
H
Takeuchi
Taku
T
Nakajima
Yoshiyuki
Y
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D015179:Colorectal Neoplasms / Q000473:pathology*; D003131:Combined Modality Therapy; D003673:Defective Viruses / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics*; D005472:Fluorouracil / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000494:pharmacology*; D006801:Humans; D007668:Kidney; D008297:Male; D017921:Mastadenovirus / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010430:Pentosyltransferases / Q000235:genetics* / Q000502:physiology; D011838:Radiation-Sensitizing Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
D000964:Antimetabolites, Antineoplastic; D001426:Bacterial Proteins; D011838:Radiation-Sensitizing Agents; D011993:Recombinant Fusion Proteins; D010430:Pentosyltransferases; C023269:uracil phosphoribosyltransferase; D005472:Fluorouracil