title: The BRCA2 gene is a potential molecular target during 5-fluorouracil therapy in human oral cancer cells.
abstract: 5-Fluorouracil (5-FU) is widely used in clinical cancer therapy. It is commonly used either alone or in combination with other drugs and/or radiation for head and neck, and other types of cancers. 5-FU induces DNA double-strand breaks (DSBs). Inhibition of the repair of 5-FU-induced DSBs may improve the therapeutic response in many tumors to this anticancer agent. The aim of the present study was to further our understanding of the pathways which are involved in the repair of 5-FU-induced DSBs. Cell survival after drug treatment was examined with colony forming assays using Chinese hamster lung fibroblast cells or Chinese hamster ovary cell lines which are deficient in DSB repair pathways involving the homologous recombination repair-related genes BRCA2 and XRCC2, and the non-homologous end joining repair-related genes DNA-PKcs and Ku80. It was found that BRCA2 was involved in such repair, and may be effectively targeted to inhibit the repair of 5-FU-induced damage. Observations showed that knockdown of BRCA2 using small interference RNA suppression increased the sensitivity to 5-FU of human oral cancer cell lines (SAS and HSC3). These findings suggest that downregulation of BRCA2 may be useful for sensitizing tumor cells during 5-FU chemotherapy.
authors.affiliation: Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Sennan-gun, Osaka 590-0494, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, Kashihara, Nara 634‑8521, Japan.
authors.forename: Atsuhisa
authors.initials: A
authors.lastname: Kajihara
authors.affiliation: Advanced Scientific Research Leaders Development Unit, Gunma University, Maebashi, Gunma 371‑8511, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Sennan-gun, Osaka 590-0494, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Kondo
authors.affiliation: Department of Radiation Oncology, School of Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Mori
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, Kashihara, Nara 634‑8521, Japan.
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Kirita
authors.affiliation: Department of Radiation Oncology, School of Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Ohnishi
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D024682:BRCA2 Protein / Q000235:genetics*; D016466:CHO Cells; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D051379:Mice; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D000964:Antimetabolites, Antineoplastic; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D034741:RNA, Small Interfering; D005472:Fluorouracil