Combined gamma-irradiation and subsequent cisplatin treatment in human squamous carcinoma cell lines sensitive and resistant to cisplatin

Purpose: To investigate the effects of combined radiation and subsequent cisplatin treatment on the human squamous carcinoma cell line SCC- 25 and its cisplatin- resistant derivative SCC- 25/ CP. Materials and methods: SCC- 25 and SCC- 25/ CP cells were treated with various gamma- ray doses ( 5 cGy - 7 Gy) followed 60 min later by cisplatin treatment and subsequently assayed for survival using a conventional colony assay. For SCC- 25, the subsequent cisplatin treatment was 0.1, 1, 10 and 20 muM for 1 h. For the more cisplatin- resistant SCC- 25/ CP cells, the subsequent cisplatin treatment was 10 and 50 muM for 1 h. Results: The cisplatin- resistant SCC- 25/ CP cells were not cross- resistant to gamma- irradiation. Subsequent treatment with an LD50 concentration of cisplatin ( 10 and 50 muM for SCC- 25 and SCC- 25/ CP, respectively) resulted in radiosensitization for SCC- 25/ CP but not for SCC- 25 cells. Gamma- irradiation of SCC- 25/ CP cells followed by treatment with 10 and 50 muM cisplatin for 1 h resulted in radiation survival curves displaying a significant low- dose hypersensitive region followed by increased radioresistance at higher doses. A total of 10 muM cisplatin resulted in radiosensitization confined to the low- dose region ( 0.05 and 0.25 Gy), whereas the higher cisplatin treatment of 50 muM resulted in the appearance of a hypersensitive region together with a reduction of the increased radioresistance region. In contrast, cisplatin treatment ( 0.1, 1, 10 and 20 mM for 1 h) of SCC- 25 cells had no significant effect on survival following 2.5 or 7.0 Gy and actually resulted in an increased low- dose radiation survival ( 0.05, 0.25 and 1 Gy) when survival was corrected for cisplatin treatment ( p < 0.01 for all cisplatin concentrations tested). Conclusions: The significant radiosensitization for SCC- 25/ CP given subsequent treatment with 50 mu M cisplatin indicates cisplatin can inhibit the increased radioresistance response in SCC- 25/ CP cells. In contrast, the subsequent cisplatin treatment of SCC- 25 cells can enhance their survival following low radiation doses.