Synergistic effects of deuterium oxide and gemcitabine in human pancreatic cancer cell lines

Abstract Purpose Pancreatic cancer still remains a treatment-refractory cancer. Standard therapy for metastatic cancer is gemcitabine (dFdC) chemotherapy. Since heavy water (deuterium oxide, D 2 O) was shown to be active in pancreatic cancer in vitro , we examined the simultaneous or sequential cytotoxic effects of D 2 O and dFdC in pancreatic cancer cell lines (AsPC-1, BxPC-3, and PANC-1). Moreover, we investigated the effect of D 2 O treatment on the colony formation of peripheral blood mononuclear cells (PBMNC) as well as the apoptosis inducing activity of D 2 O and dFdC and the regulation of tumor suppressor gene p21. Results Simultaneous incubation of human pancreatic carcinoma cells with D 2 O and dFdC led to a decrease of IC 50 values of dFdC alone in all cell lines examined. Sequential application of D 2 O and dFdC caused synergistic effects. Treatment with 10–30% D 2 O did not show any significant inhibition effects on the colony formation of peripheral blood mononuclear cells (PBMNC), indicating limited adverse effects of D 2 O on bone marrow cells. Treatment with D 2 O in combination with dFdC significantly ( p As the combination of D 2 O and dFdC might offer an additional option for the control of pancreatic cancer, this treatment should be investigated in a pancreas carcinoma animal model in order to scrutinize the in vitro data.