Metformin is a biguanide derivative that is widely used in the treatment of diabetes mellitus. One of the pharmacological targets of metformin is adenosine monophosphate-activated protein kinase (AMPK). We investigated the effect of metformin on the suppression of intestinal polyp formation in Apc

Background and aims:The effect of adiponectin on colorectal carcinogenesis has been proposed but not fully investigated. We investigated the effect of adiponectin deficiency on the development of colorectal cancer.Methods:We generated three types of gene-deficient mice (adiponectin-deficient, adiponectin receptor 1-deficient, and adiponectin receptor 2-deficient) and investigated chemical-induced colon polyp formation and cell proliferation in colon epithelium. Western blot analysis was performed to elucidate the mechanism which affected colorectal carcinogenesis by adiponectin deficiency.Results:The numbers of colon polyps were significantly increased in adiponectin-deficient mice compared with wild-type mice fed a high-fat diet. However, no difference was observed between wild-type and adiponectin-deficient mice fed a basal diet. A significant increase in cell proliferative activity was also observed in the colonic epithelium of the adiponectin-deficient mice when compared with wild-type mice fed a high-fat diet; however, no difference was observed between wild-type and adiponectin-deficient mice fed a basal diet. Similarly, an increase in epithelial cell proliferation was observed in adiponectin receptor 1-deficient mice, but not in adiponectin receptor 2-deficient mice. Western blot analysis revealed activation of mammalian target of rapamycin, p70 S6 kinase, S6 protein and inactivation of AMP-activated protein kinase in the colon epithelium of adiponectin-deficient mice fed with high-fat diet.Conclusions:Adiponectin suppresses colonic epithelial proliferation via inhibition of the mammalian target of the rapamycin pathway under a high-fat diet, but not under a basal diet. These studies indicate a novel mechanism of suppression of colorectal carcinogenesis induced by a Western-style high-fat diet.

Abstract. Adiponectin is secreted by adipocytes and is a key hormone responsible for insulin sensitization. Recent studies have shown that plasma adiponectin is decreased in patients with breast, endometrial and gastric cancer. However, the effect of adiponectin on colorectal carcinogenesis is controversial. It is now well known that the adiponectin receptor exists in two isoforms, adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). We

Esophageal cancer is difficult to treat because of its rapid progression, and more effective therapeutic approaches are needed. The PPARγ γ γ γ is a nuclear receptor superfamily member that is expressed in many cancers. PPARγ γ γ γ expression is a feature of esophageal cancer cell lines, and in the present investigation, the PPARγ γ γ γ antagonists T0070907 and GW9662 could induce loss of invasion but could not induce growth reduction or apoptosis at low concentrations (<10 mM). A high concentration of antagonists (50 µ µ µ µM) inhibited cell growth and induced apoptosis, but these effects did not explain our result at the low concentration. Morphological change, decreased expression of the cell signaling pathway and inhibition of cancer cell invasion were observed in the low concentration. This suggested that PPARγ γ γ γ antagonists inhibited esophageal cancer cell invasion as well as cell adherence, most likely due to alteration in the FAK-MAPK pathway, and this was independent of apoptosis. These results suggested that PPARγ γ γ γ plays an important role in cancer cell invasion and that it might be a novel target for therapy of esophageal cancer. (Cancer Sci 2006; 97: 854-860)

Peroxisome proliferator-activated receptor g (PPARg) is a ligandactivated transcription factor that has been implicated in the carcinogenesis and progression of various solid tumors, including pancreatic carcinomas. We aimed to clarify the role of this receptor in pancreatic cell motility in vitro and in metastasis in vivo. P ancreatic ductal adenocarcinoma is associated with one of the highest mortality rates in patients with malignancies.