RRC ID 37070
Author Kobashigawa S, Morikawa K, Mori H, Kashino G.
Title Gemcitabine Induces Radiosensitization Through Inhibition of RAD51-dependent Repair for DNA Double-strand Breaks.
Journal Anticancer Res.
Abstract BACKGROUND/AIM:Gemcitabine (GEM) is used in clinical chemo-radiotherapy; however, the mechanism that contributes to enhanced radiosensitivity by GEM is not fully-understood. We evaluated the effect of GEM on radiosensitization in pancreatic cancer cell lines.
MATERIALS AND METHODS:Pancreatic cell lines PK-59 and PK-45p were used. A total of 5 μM GEM for 4 h were administered pre- or post-gamma irradiation.
RESULTS:Enhanced cell killing effects by GEM in radiotherapy were observed for pre-treatment but not post-treatment GEM. We focused on the dynamics of RAD51 and phospho-H2AX foci after irradiation. Significantly higher numbers of phospho-H2AX foci were observed in GEM pre-treated cells than in untreated cells after irradiation. We also found inhibition of the formation and degradation of RAD51 foci by GEM pre-treatment. The radiosensitizing effect of GEM was suppressed by knockdown of RAD51.
CONCLUSION:RAD51-dependent homologous recombination is one of the key targets in the GEM-induced radiosensitizing effect.
Volume 35(5)
Pages 2731-7
Published 2015-5
PII 35/5/2731
PMID 25964552
MeSH Cell Line, Tumor DNA Breaks, Double-Stranded / drug effects DNA Repair / drug effects Deoxycytidine / administration & dosage Deoxycytidine / analogs & derivatives* Gamma Rays Humans Pancreatic Neoplasms / drug therapy* Pancreatic Neoplasms / pathology Pancreatic Neoplasms / radiotherapy* Radiation Tolerance / drug effects* Radiation-Sensitizing Agents
IF 1.865
Times Cited 4
Human and Animal Cells PK-59(RCB1901) PK-45P(RCB2141)