Effect of treatment schedule on the interaction of Cisplatin and radiation in human lung cancer cells.

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.