Ricerc@Sapienza

Cigarette smoking is a recognized risk factor for colon cancer and nicotine, the
principal active component of tobacco, plays a pivotal role in increasing colon cancer
cell growth and survival. The aim of this study was to determine the effect of
nicotine on cellular Caco-2 and HCT-8 migration and invasion, focusing on epithelial
to mesenchymal transition (EMT) induction, and COX-2 pathway involvement. In
both these cell lines, treatment with nicotine increased COX-2 expression and the
release of its enzymatic product PGE2. Moreover, nicotine-stimulated cells showed
increased migratory and invasive behavior, mesenchymal markers up-regulation and
epithelial markers down-regulation, nuclear translocation of the β-catenin, increase
of MMP-2 and MMP-9 activity, and enhanced NF-κB expression. Noticeably, all
these effects are largely mediated by COX-2 activity, as simultaneous treatment of
both cell lines with nicotine and NS-398, a selective COX-2 inhibitor, greatly
reduced the number of migrating and invading cells and reverted nicotine-induced
EMT. These findings emphasize that nicotine triggers EMT, leading hence to
increased migration and invasiveness of colon cancer cells. Thereby, the use of
COX-2 inhibitor drugs might likely counteract nicotine-mediated EMT effects on
colon cancer development and progression