Nicotine promoted colon cancer growth via epidermal growth factor receptor, c-Src, and 5-lipoxygenase-mediated signal pathway

Nicotine [3-(1-methyl-2-pyrrolidinyl)-pyridine], a major alkaloid in tobacco, has been implicated as playing a role in carcino-genesis. Our previous study showed that passive cigarette smoking promoted inflammation-associated colonic adenoma formation in mice, and 5-lipoxygenase (5-LOX) plays an impor-tant role in this process. In the present study, we aimed to investigate whether nicotine could stimulate colon cancer cell proliferation and tumor growth in nude mice xenograft model and the possible mechanisms involved. Results showed that nicotine stimulated SW1116 colon cancer cell proliferation in a dose-dependent manner. Epidermal growth factor receptor (EGFR) and c-Src phosphorylation levels together with protein expression of 5-LOX were also significantly enhanced in this proliferation process. Inhibitors of EGFR and c-Src alleviate