Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice

International Journal of Molecular Sciences

Koki Obara¹  Yohei Shirakami¹  Takahiro Kochi¹  Kazufumi Fukuta¹  Akinori Maruta¹  Masahito Shimizu¹  Masaya Kubota¹  Soichi Iritani¹  Hiroyasu Sakai¹  Nobuhiko Nakamura¹  Takuji Tanaka² 

[1] Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan;Department of Pathological Diagnosis, Gifu Municipal Hospital, Gifu 500-8513, Japan;

关键词: colorectal cancer;    pentoxifylline;    chemoprevention;    obesity;    oxidative stress;    inflammation;   

DOI  :  10.3390/ijms18020413

来源: DOAJ

【 摘 要 】

Obesity and its related metabolic abnormalities, including enhanced oxidative stress and chronic inflammation, are closely related to colorectal tumorigenesis. Pentoxifylline (PTX), a methylxanthine derivative, has been reported to suppress the production of tumor necrosis factor (TNF)-α and possess anti-inflammatory properties. The present study investigated the effects of PTX on the development of carcinogen-induced colorectal premalignant lesions in obese and diabetic mice. Male C57BL/KsJ-db/db mice, which are severely obese and diabetic, were administered weekly subcutaneous injections of the colonic carcinogen azoxymethane (15 mg/kg body weight) for four weeks and then received drinking water containing 125 or 500 ppm PTX for eight weeks. At the time of sacrifice, PTX administration markedly suppressed the development of premalignant lesions in the colorectum. The levels of oxidative stress markers were significantly decreased in the PTX-treated group compared with those in the untreated control group. In PTX-administered mice, the mRNA expression levels of cyclooxygenase (COX)-2, interleukin (IL)-6, and TNF-α, and the number of proliferating cell nuclear antigen (PCNA)-positive cells in the colonic mucosa, were significantly reduced. These observations suggest that PTX attenuated chronic inflammation and oxidative stress, and prevented the development of colonic tumorigenesis in an obesity-related colon cancer model.

【 授权许可】

Unknown