A mechanistic study of colon cancer growth promoted by cigarette smoke extract

Substantial evidence indicates that significant exposure to cigarette smoke is associated with an elevated risk for colorectal cancer. However, the mechanisms underlying the causal relationship between cigarette smoking and colorectal cancer remain to be investigated. Our previous study showed that cigarette smoke promotes the formation of inflammation-associated colonic adenoma in mice through an angiogenic pathway. Therefore, in the present study, we used the human colon adenocarcinoma cell line, SW1116, and human umbilical vascular endothelial cells (HUVECs) to elucidate the possible mechanisms in vitro. Results showed that cigarette smoke extract enhanced cell proliferation and the expression of 5-lipoxygenase (5-LOX), vascular endothelium growth factor (VEGF), matrix metalloproteinases (MMPs) 2 and 9 in SW1116 cells. Inhibition of 5-LOX decreased cell proliferation and expressions of VEGF, MMP-2 and MMP-9 induced by cigarette smoke extract. In addition, cigarette smoke extract indirectly stimulated HUVEC proliferation, a biological activity closely related to angiogenesis during tumor growth. This was again blocked by the 5-LOX inhibitor. Taken together, the results of the present study demonstrate the central role of 5-LOX and its relationship with angiogenic mediators in the actions of cigarette smoke in the promotion of angiogenesis during colon cancer growth. (c) 2005 Elsevier B.V. All rights reserved.