Our studies support an innovative application of available PARP inhibitors or new cytoplasmic PARP-1 antagonists to enhance TRAIL therapy for TRAIL-resistant pancreatic cancers.
The present study explored the possibility of sensitizing pancreatic cancer to gemcitabine chemotherapy by combining the chemotherapy with the proapoptotic genes Bax and TNF-related apoptosis-inducing ligand (TRAIL).
TRAIL treatment increased ROS in two TRAIL-sensitive pancreatic cancer cell lines, MiaPaCa-2 and BxPC-3, but ROS were involved in TRAIL-induced apoptosis only in MiaPaCa-2 cells.
<b>Methods:</b> Starting from the BXPC3 cell line, we generated and profiled a TRAIL-resistant model of pancreatic cancer, testing the impact of the combined treatment <i>in vitro</i> with specific cytotoxicity and metabolic assays.
These findings show that pancreatic cancers are insensitive towards TRAIL-mediated apoptosis despite expression of TRAIL and its receptors, suggesting the presence of mediators which inhibit the TRAIL cell-death-inducing pathway in pancreatic cancer cells.
Our results suggest that TRAIL gene therapy in combination with gemcitabine might be a useful therapeutic approach for treating metastatic pancreatic cancers.
These results indicate that Bcl-xL is responsible for TRAIL resistance in human pancreatic cancer cells, and that Bcl-2 family inhibitors could represent promising reagents to sensitize human pancreatic cancers in DR-targeting therapy.
Our results indicate that MUC5AC inhibits TRAIL‑induced apoptosis in human pancreatic cancer and may serve as an important indicator in diagnosis and prognosis.
We found that the novel CTL harboring Lenti/hCD40L/E1AB and Ad5/35-TRAIL inhibited pancreatic cancer cell growth and angiogenesis in vitro and in vivo.