Suppressive Effect of Pioglitazone, a PPAR Gamma Ligand, on Azoxymethane-induced Colon Aberrant Crypt Foci in KK-A Mice

Ueno, Toshiya; Teraoka, Naoya; Takasu, Shinji; Nakano, Katsuya; Takahashi, Mami; Yamamoto, Masafumi; Fujii, Gen; Komiya, Masami; Yanaka, Akinori; Wakabayashi, Keiji; Mutoh, Michihiro

추천

검색

자료유형: 학술저널

저자정보: Ueno, Toshiya (Division of Cancer Prevention Research, National Cancer Center Research Institute) Teraoka, Naoya (Division of Cancer Prevention Research, National Cancer Center Research Institute) Takasu, Shinji (Division of Cancer Prevention Research, National Cancer Center Research Institute) Nakano, Katsuya (Division of Cancer Prevention Research, National Cancer Center Research Institute) Takahashi, Mami (Central Animal Division, National Cancer Center Research Institute) Yamamoto, Masafumi (Central Animal Division, National Cancer Center Research Institute) Fujii, Gen (Division of Cancer Prevention Research, National Cancer Center Research Institute) Komiya, Masami (Division of Cancer Prevention Research, National Cancer Center Research Institute) Yanaka, Akinori (Faculty of Pharmaceutical Sciences, Tokyo University of Science) Wakabayashi, Keiji (Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka) Mutoh, Michihiro (Division of Cancer Prevention Research, National Cancer Center Research Institute)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제13권 제8호

발행연도: 2012.1

수록면: 4,067 - 4,073 (7page)

이용수

📌

연구주제

📖

연구배경

🔬

연구방법

🏆

연구결과

초록· 키워드

오류제보하기

Obesity is an established risk factor for colorectal cancer. Pioglitazone is a peroxisome proliferator activated receptor$receptor{\gamma}$ ($PPAR{\gamma}$) agonist that induces differentiation in adipocytes and induces growth arrest and/or apoptosis in vitro in several cancer cell lines. In the present study, we investigated the effect of pioglitazone on the development of azoxymethane-induced colon aberrant crypt foci (ACF) in KK-$A^{\mathcal{Y}}$ obesity and diabetes model mice, and tried to clarify mechanisms by which the $PPAR{\gamma}$ ligand inhibits ACF development. Administration of 800 ppm pioglitazone reduced the number of colon ACF/mouse to 30% of those in untreated mice and improved hypertrophic changes of adipocytes in KK-$A^{\mathcal{Y}}$ mice with significant reduction of serum triglyceride and insulin levels. Moreover, mRNA levels of adipocytokines, such as leptin, monocyte chemoattractant protein-1 and plasminogen activator inhibitor-1, in the visceral fat were decreased. PCNA immunohistochemistry revealed that pioglitazone treatment suppressed cell proliferation in the colorectal epithelium with elevation of p27 and p53 gene expression. These results suggest that pioglitazone prevented obesity-associated colon carcinogenesis through improvement of dysregulated adipocytokine levels and high serum levels of triglyceride and insulin, and increase of p27 and p53 mRNA levels in the colorectal mucosa. These data indicate that pioglitazone warrants attention as a potential chemopreventive agent against obesity-associated colorectal cancer.

#Pioglitazone #obesity #PPAR gamma #aberrant crypt foci

참고문헌 (0)

참고문헌 신청

참고문헌이 DBpia에서 서비스 중이라면, [참고문헌 신청]을 통해 등록해보세요