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©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Nov 14, 2008; 14(42): 6473-6480
Published online Nov 14, 2008. doi: 10.3748/wjg.14.6473
Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by azoxymethane in mice
Tamao Nishihara, Miyako Baba, Morihiro Matsuda, Masahiro Inoue, Yasuko Nishizawa, Atsunori Fukuhara, Hiroshi Araki, Shinji Kihara, Tohru Funahashi, Shinji Tamura, Norio Hayashi, Hiroyasu Iishi, Iichiro Shimomura
Tamao Nishihara, Hiroshi Araki, Shinji Tamura, Norio Hayashi, Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, 2-2, Yamada-oka, Suita, Osaka 565-0871, Japan
Miyako Baba, Yasuko Nishizawa, Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Research Institute, 1-3-2, Nakamichi, Higashinari-ku, Osaka 537-8511, Japan
Morihiro Matsuda, Atsunori Fukuhara, Shinji Kihara, Tohru Funahashi, Iichiro Shimomura, Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamada-oka, Suita, Osaka 565-0871, Japan
Masahiro Inoue, Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Research Institute, 1-3-2, Nakamichi, Higashinari-ku, Osaka 537-8511, Japan
Hiroyasu Iishi, Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka 537-8511, Japan
Author contributions: Nishihara T and Baba M contributed equally to this work; Nishihara T, Baba M, Matsuda M, Inoue M, Fukuhara A, Kihara S, Funahashi T, Tamura S, Iishi H, and Shimomura I designed the research; Nishihara T, Baba M, and Araki H performed the research; Nishihara T, Baba M, and Nishizawa Y analyzed the data; Nishihara T, Matsuda M, Fukuhara A, Hayashi N, and Shimomura I wrote the paper.
Supported by A grant from Foundation for Promotion of Cancer Research in Japan
Correspondence to: Tamao Nishihara, MD, PhD, Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan. tamaon@gh.med.osaka-u.ac.jp
Telephone: +81-6-68793621 Fax: +81-6-68793629
Received: June 21, 2008
Revised: October 20, 2008
Accepted: October 27, 2008
Published online: November 14, 2008
AIM: To investigate the causal relationship between hypoadiponectinemia and colorectal carcinogenesis in in vivo experimental model, and to determine the contribution of adiponectin deficiency to colorectal cancer development and proliferation.
METHODS: We examined the influence of adiponectin deficiency on colorectal carcinogenesis induced by the administration of azoxymethane (AOM) (7.5 mg/kg, intraperitoneal injection once a week for 8 wk), by using adiponectin-knockout (KO) mice.
RESULTS: At 53 wk after the first AOM treatment, KO mice developed larger and histologically more progressive colorectal tumors with greater frequency compared with wild-type (WT) mice, although the tumor incidence was not different between WT and KO mice. KO mice showed increased cell proliferation of colorectal tumor cells, which correlated with the expression levels of cyclooxygenase-2 (COX-2) in the colorectal tumors. In addition, KO mice showed higher incidence and frequency of liver tumors after AOM treatment. Thirteen percent of WT mice developed liver tumors, and these WT mice had only a single tumor. In contrast, 50% of KO mice developed liver tumors, and 58% of these KO mice had multiple tumors.
CONCLUSION: Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by AOM in mice. This study strongly suggests that hypoadiponectinemia could be involved in the pathogenesis for colorectal cancer and liver tumor in human subjects.
