Abstract 152: Nicotine inhibits the therapeutic effects of gemcitabine in pancreatic cancer cells in vitro and in a mouse xenograft model

Pancreatic cancer is a leading cause of cancer deaths in developed countries. The nucleoside analog Gemcitabine, which induces apoptosis, is widely used for the therapy of pancreatic cancer. Smoking is an established risk factor for pancreatic cancer and nicotine replacement therapy often accompanies chemotherapy. Using the two human pancreatic cancer cell lines PANC-1 and BXPC-3 in vitro, our data show that low concentrations of nicotine significantly reduces the growth inhibiting effects of gemcitabine while also significantly inhibiting gemcitabine-induced apoptosis as indicated by determination of cleaved caspase-3 in immunoassays. Analysis of other signaling proteins is currently in progress. In a mouse xenograft model with BXPC-3 cells, a 1 micromolar concentration of nicotine in the drinking water significantly reduced the therapeutic response to gemcitabine while additionally reducing the induction of pro-apoptotic proteins and the inhibition of growth stimulating proteins by gemcitabine. Our data suggest that nicotine replacement therapy and possibly also the exposure to second hand smoke may negatively impact therapeutic outcomes of gemcitabine in pancreatic cancer patients. Nicotine addiction should be treated with non nicotine agents in such patients and exposure to tobacco smoke in any form should be avoided. Supported by grants RO1CA130888 and RO1CA042829 with the National Cancer Institute. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 152. doi:1538-7445.AM2012-152