title: Effect of treatment schedule on the interaction of Cisplatin and radiation in human lung cancer cells.
abstract: This study was designed to determine the effects of the treatment schedule on the interaction between cisplatin and radiation. Cells of a human squamous cell lung cancer cell line were treated with cisplatin and radiation using three treatment protocols: 1-h exposure to cisplatin immediately followed by irradiation (A), 4-day continuous exposure to cisplatin immediately followed by irradiation (B), and 1-h exposure to cisplatin followed by irradiation after a 4-day interval (C). The interactions were assessed by isobologram, cell cycle distribution and apoptosis. The combination resulted in a additive effect in every protocol. Cell cycle accumulation at G(2)/M phase before irradiation was observed in Protocols B and C, whereas no cell cycle shift in the limited time course was noted in Protocol A. Although a 4-day continuous exposure to cisplatin and a 1-h exposure to cisplatin followed by a 4-day interval before irradiation caused significantly increased apoptosis, an additional increase in apoptosis after irradiation was not observed in Protocols B and C, whereas Protocol A showed an additional increase. Despite a cell cycle shift favoring radiation sensitivity, the drug-radiation interactions in Protocols B and C were additive, possibly because of negative effects including induction of a durable G(2)/M-phase arrest and suppression of apoptosis by cisplatin.
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Asaka-Amano
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Takiguchi
authors.forename: Mari
authors.initials: M
authors.lastname: Yatomi
authors.forename: Katsushi
authors.initials: K
authors.lastname: Kurosu
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kasahara
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Tanabe
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tatsumi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kuriyama
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000628:therapy*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage*; D019583:Dose Fractionation, Radiation; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000628:therapy*; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D018714:Radiotherapy, Adjuvant
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D002945:Cisplatin