Contributory role of 5-lipoxygenase and its association with angiogenesis in the promotion of inflammation-associated colonic tumorigenesis by cigarette smoking.
Our previous study shows that cigarette smoking can promote inflammation-associated adenoma formation in the mouse colon, but the underlying mechanism remains unknown. Several studies suggest that there is a link between 5-lipoxygenase (5-LOX) and carcinogenesis in humans and animals. In the present study, we aims to investigate whether the promoting action of cigarette smoke on inflammation-associated colon cancer formation is associated with 5-LOX activation in mice. Results showed that exposure to the mainstream smoke of unfiltered cigarettes enhanced the 5-LOX protein expression in the inflammation-associated colonic adenomas. It was accompanied with an up-regulation of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF). Both are the key angiogenic factors for tumorigenesis. 5-LOX inhibitors decreased the incidence of colonic adenoma formation and reduced angiogenesis, MMP-2 activity and VEGF protein expression in the colons of these animals. Taken together, these results strongly suggest that cigarette smoke can induce 5-LOX expression which plays an important role in activation of MMP-2 and VEGF to induce angiogenic process and promotion of inflammation-associated adenoma formation in mice.
Ye
Yi-Ni
YN
Department of Pharmacology, Faculty of Medicine, Zhejiang University, Hangzhou, China.
Liu
Edgar Shiu-Lam
ES
Shin
Vivian Yvonne
VY
Wu
William Ka-Kei
WK
Cho
Chi-Hin
CH
D000236:Adenoma / Q000209:etiology / Q000473:pathology*; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000096:biosynthesis / Q000502:physiology*; D015153:Blotting, Western; D003093:Colitis, Ulcerative / Q000139:chemically induced; D003110:Colonic Neoplasms / Q000209:etiology / Q000473:pathology*; D003911:Dextrans; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007249:Inflammation / Q000209:etiology / Q000473:pathology*; D007413:Intestinal Mucosa / Q000473:pathology; D016859:Lipoxygenase Inhibitors; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D012907:Smoking / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D003911:Dextrans; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D001094:Arachidonate 5-Lipoxygenase; D020778:Matrix Metalloproteinase 2