Curcumin Augments Gemcitabine Cytotoxic Effect on Pancreatic Adenocarcinoma Cell Lines

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Abstract
Gemcitabine, the first-line agent in pancreatic adenocarcinoma, has shown limited clinical benefit. Cyclooxygenase-2 (COX-2) represent one of the most promising targets for cancer prevention and treatment. In this study, we investigated whether the phytochemical curcumin, a natural COX-2 inhibitor, can potentiate gemcitabine effect on survival of human pancreatic cancer cells. P34 (high COX-2 expression) and Panc-1 (low COX-2 expression) pancreatic cancer cell lines were exposed to different concentrations of gemcitabine (0.1-10 microM), curcumin (0-50 microM), and their combination. Cell viability was evaluated by XTT assay. Cell cycle and apoptosis were assessed by flow cytometry. COX-2, EGFR, and p-ERK1/2 expression was measured by Western blot analysis. Curcumin increased the inhibitory effect of gemcitabine on cell viability as well as its pro-apoptotic effect in COX-2 positive, p34 cells, but not in COX-2 negative, Panc-1 cells. In p34 cells, combination of curcumin and gemcitabine downregulated both COX-2 and p-ERK1/2 in a dose-dependent manner. The increased cytotoxic effect of the combination on cell survival and on the induction of apoptosis in COX-2 expressing pancreatic cancer cells is probably associated with downregulation of COX-2 and p-ERK1/2 levels. This finding may contribute to the development of an effective treatment of pancreatic adenocarcinoma.