Synergistic cytotoxic effect of TRAIL and gemcitabine in pancreatic cancer cells

Background: Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a novel member of the TNF family and triggers apoptosis in a variety of malignant cells. Materials and Methods: We assessed the antitumour activity of TRAIL in six human pancreatic cancer cell lines by measuring apoptosis with sulforhodamine B cytotoxicity assays, DAPI staining and FACScans. Results: All six cell lines were sensitive to TRAIL-induced apoptosis. The expression levels of TRAIL receptors R1, R2, R3 and R4 did not correlate with TRAIL sensitivity. Simultaneous treatment with TRAIL and the chemotherapeutic agent gemcitabine had a synergistic effect. Caspase-8 and -3 activities were increased by TRAIL treatment and apoptosis was largely blocked by caspase-8 and -3 inhibitors. Conclusion: Apoptotic cell death can be induced in pancreatic cancer cells by TRAIL treatment and this may be mediated through activation of caspases-8 and -3. Gemcitabine significantly increased the antitumour effect of TRAIL, suggesting novel therapeutic approaches.