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 (mu)M for 1 h. For the more cisplatin-resistant SCC-25/CP cells, the subsequent cisplatin treatment was 10 and 50 (mu)M 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 (mu)M for SCC-25 and SCC25/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 (mu)M 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 (mu)M cisplatin resulted in radiosensitization confined to the low-dose region (0.05 and 0.25 Gy), whereas the higher cisplatin treatment of 50 (mu)M 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 (mu)M 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.