Cigarette smoking is a putative environmental risk factor for colon cancer. Nicotine, an active alkaloid in tobacco, has been implicated in carcinogenesis. In the present study, we demonstrated that oral nicotine administration (50 or 200 μg/ml) for 25 days stimulated growth of human colon cancer xenograft in nude mice. It also increased vascularization in the tumors and elevated cotinine and adrenaline plasma levels. β-Adrenoceptors, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and vascular endothelial growth factor (VEGF) in tumor tissues were also increased by nicotine. I.p. injection of β1-selective antagonist (atenolol, 5 or 10 mg/kg) or β2-selective antagonist (ICI 118,551, 5, or 10 mg/kg) blocked the nicotine-stimulated tumor growth dose dependently, in which β2-selective antagonist produced a more prominent effect. β-Adrenoceptors blockade also abrogated the stimulatory action of nicotine on microvessel densities as well as cell expression of COX-2, PGE2, and VEGF, in which β2-selective antagonist produced a significant effect. These findings provide a direct evidence that nicotine can enhance colon tumor growth mediated partly by stimulation of β-adrenoceptors, preferentially the β2-adrenoceptors. Activation of β-adrenoceptors and the subsequent stimulation of COX-2, PGE2, and VEGF expression is perhaps an important mechanism in the tumorigenic action of nicotine on colon tumor growth. These data suggest that β-adrenoceptors play a modulatory role in the development of colon cancer and partly elucidate the carcinogenic action of cigarette smoke.
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Wong et al. (2007) studied this question.