title: Significance of scheduling on the cytotoxicity of radiation and cisplatin combination treatment in nasopharyngeal carcinoma cells.
abstract: The use of cisplatin as a potential radiosensitizer in nasopharyngeal carcinoma (NPC) has produced encouraging results in clinical trials. In order to provide information on improving the design of clinical treatments, we investigated the effect of cisplatin dose, and the time interval and sequence between administration of cisplatin and radiation on cell survival of two NPC cell lines, CNE1 and SUNE1. When cisplatin was applied first, an exposure time of 24 h resulted in up to 2.6-fold increase in cell death and 7-fold increase in radiation effect (cell survival after cisplatin/cell survival after cisplatin plus radiation) in the cisplatin-radiation combination treatment compared to the cells treated with cisplatin for 4 h. When radiation was applied first, a shorter interval time of 4 h followed by cisplatin treatment resulted in up to 3-fold increase in cell death and a 3-fold enhanced radiation effect over longer time intervals of 24 h. By changing the order of radiation and cisplatin treatment alone, a 2-fold difference in radiation effect was observed. The differential cytotoxicity was partially explained by the alterations in cell cycle distribution. Our results indicate the importance of scheduling the radiation and cisplatin combination regimens on the survival of NPC cells.
authors.affiliation: Department of Anatomy, University of Hong Kong, SAR, China. xhwang@hkucc.hku.hk
authors.forename: Xianghong
authors.initials: X
authors.lastname: Wang
authors.forename: Lillian S N
authors.initials: LS
authors.lastname: Chow
authors.forename: John M
authors.initials: JM
authors.lastname: Nicholls
authors.forename: Dora L W
authors.initials: DL
authors.lastname: Kwong
authors.forename: Jonathan S T
authors.initials: JS
authors.lastname: Sham
authors.forename: Y C
authors.initials: YC
authors.lastname: Wong
authors.forename: Sai Wah
authors.initials: SW
authors.lastname: Tsao
mesh_terms: D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
chemical_list: D011838:Radiation-Sensitizing Agents; D002945:Cisplatin