Abstract | PURPOSE: Non-steroidal anti-inflammatory drugs, including sulindac, have been shown to exhibit anti- colon cancer activity; however, the detailed mechanisms concerning continuous long-term administration are still unclear. Therefore, we examined the anti-colon carcinogenesis effects of sulindac after prolonged administration. METHODS: Administration of AOM, a colon-specific carcinogen, induced colonic preneoplastic lesions, which can progress to carcinomas about 40-50 weeks after AOM administration. We studied the effects of sulindac on the incidence of preneoplastic lesions, proliferative activity of colonic cells ( AgNORs), tumor suppressor adenomatous polyposis coli (APC) gene expression, and apoptosis using AOM-treated rat colon mucosa at 4 weeks and 40 weeks (early and late stage of colon carcinogenesis, respectively). RESULTS:
Sulindac suppressed the development of preneoplastic lesions induced by AOM at 4 weeks and 40 weeks by about 50% ( P<0.01); the proliferative activity of colonic cells increased by AOM was suppressed almost completely. Furthermore, APC expression was significantly increased by sulindac at both the early and late stages ( P<0.01). However, apoptosis was clearly increased at the early stage ( P<0.01), but not at the late stage. CONCLUSIONS:
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Authors | Y Kishimoto, K Yashima, T Morisawa, T Ohishi, A Marumoto, A Sano, Y Idobe-Fujii, N Miura, G Shiota, Y Murawaki, J Hasegawa |
Journal | Journal of cancer research and clinical oncology
(J Cancer Res Clin Oncol)
Vol. 128
Issue 11
Pg. 589-95
(Nov 2002)
ISSN: 0171-5216 [Print] Germany |
PMID | 12458338
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adenomatous Polyposis Coli Protein
- Cyclooxygenase Inhibitors
- RNA, Messenger
- Sulindac
- Azoxymethane
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Topics |
- Adenomatous Polyposis Coli Protein
(genetics)
- Animals
- Apoptosis
- Azoxymethane
(toxicity)
- Colon
(drug effects, metabolism)
- Colonic Neoplasms
(metabolism, pathology, prevention & control)
- Cyclooxygenase Inhibitors
(administration & dosage)
- In Situ Nick-End Labeling
- Intestinal Mucosa
(drug effects, metabolism)
- Male
- Nucleolus Organizer Region
(metabolism)
- Precancerous Conditions
(metabolism, pathology, prevention & control)
- RNA, Messenger
(metabolism)
- Rats
- Rats, Inbred F344
- Reverse Transcriptase Polymerase Chain Reaction
- Sulindac
(administration & dosage)
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