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

Abstract

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