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


OBJECTIVE
To examine the radiosensitivity of human pancreatic cancer cells and its modulation by 5-FU.


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.


CONCLUSIONS
Both pulse and continuous exposure increase radiation cell killing, but only continuous exposure may radiosensitize MiaPaCa-2 cells.
Department of Radiation Oncology, Institut de Recerca, Hospital de la Santa Creu i Sant Pau Av. Sant Antoni M. Claret, 167 E-08025 Barcelona, Spain. jbalart@hsp.santpau.es
Josep
J
Balart
Gabriel
G
Capellà
Rosa M
RM
de los Inocentes
Javier
J
de Andrés
Carme
C
Ares
Jordi
J
Craven-Bartle
Fèlix
F
Lluís
D000230:Adenocarcinoma; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010190:Pancreatic Neoplasms; D011878:Radiotherapy; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil