Treatment with 5-fluorouracil enhances radiosensitivity of the human pancreatic cancer cell line MiaPaCa-2

Background and Purpose: Several clinical studies have suggested that the combination of radiation therapy and 5-fluorouracil (5-FU) may improve outcome of patients with pancreatic cancer. However, there are few experimental studies supporting this treatment. Aim of the Study: To examine the radiosensitivity of human pancreatic cancer cells and its modulation by 5-FU. Material and Methods: MiaPaCa-2, PANC-1 and NP-18 cells growing as monolayer culture were treated with radiation and 5-FU. In addition, 5-FU was studied administered either pre- or postradiation, both as pulse or continuous exposure. Cell survival was determined by the in vitro clonogenic assay. Results: In MiaPaCa-2 cell line, both radiation and 5-FU alone reduced cell survival. The addition of 5-FU to radiation caused a significant net decrease of cell survival. Pulse exposure of 5-FU decreased survival after 2 Gy and mean inactivation dose by 1.64; continuous exposure decreased survival after 2 Gy and mean inactivation dose by about 2.4. Timing of 5-FU exposure did not modify survival. However, when adjusting for 5-FU killing effect and cell multiplicity, only continuous exposure significantly enhanced radiation cell killing. Conclusion: Both pulse and continuous exposure increase radiation cell killing, but only continuous exposure may radiosensitize MiaPaCa-2 cells.