gms | German Medical Science

Introduction: Pancreatic cancer is still a devastating malignancy with a 5-year survival of only 5%. For 25 years treatment success has remained largely unchanged demonstrating the resistance of pancreatic cancer cells to conventional chemotherapy. The development of targeted therapies towards the molecular aberrations responsible for apoptosis evasion is of paramount importance.

Material and methods: The sensitivity of various pancreatic cancer cell lines to several chemotherapeutics was investigated by growth and apoptosis assays. Expression profiles of various genes were performed by RT-PCR and Western Blot analysis to determine the influence of apoptosis dysregulation and resulting resistances to chemotherapeutics. To improve gemcitabine-induced apoptosis several candidate genes were silenced with siRNA simultaneously.

Results: Pancreatic cancer cells show resistance towards gemcitabine treatment despite high concentrations. By simultaneous gene silencing of dysregulated apoptosis genes in combination with low-dose gemcitabine treatment the PDAC cells were resensitized to this medication.

Conclusion: Molecular aberrations and special intracellular regulation mechanisms of PDAC cells in response to gemcitabine treatment, especially within the apoptosis pathway, might play an important role for their resistance. Targeted simultaneous silencing of apoptosis genes resensitized PDAC cells. This enables a multimodal therapy with low-dose gemcitabine treatment.