Figure 6

Gemcitabine sensitivity of Panc02 cells in vitro. (A) Effect of thrombin stimulation on gemcitabine sensitivity of Panc02 pancreatic cancer cells. (B) Conditioned medium (CM) collected from tumor-associated fibroblasts did not affect gemcitabine efficiency (left panel), and thrombin-stimulated tumor-associated fibroblasts did not enhance gemcitabine resistance (right panel). (C) Effect of gemcitabine on cell viability (left panel) and proliferation (right panel) of Panc02 cells in the presence or absence of growth factors. Shown are the means ± SEM of three experiments performed in sixplo. (D) Proposed mechanism by which dabigatran potentiates gemcitabine-induced growth inhibition of pancreatic cancers. Dabigatran reduces thrombin production, which (1) subsequently leads to increased angiogenesis and (2) subsequently increases proliferation of tumor cells. Highly proliferative tumor cells are finally efficiently killed by gemcitabine (3).