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


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 microM for 1 h. For the more cisplatin-resistant SCC-25/CP cells, the subsequent cisplatin treatment was 10 and 50 microM 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 microM 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 microM 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 microM cisplatin resulted in radiosensitization confined to the low-dose region (0.05 and 0.25 Gy), whereas the higher cisplatin treatment of 50 microM 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 microM 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 microM 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.
Caney
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Department of Physics and Astronomy, McMaster University, Hamilton, Ontario, Canada.
Singh
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Lukka
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Rainbow
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AJ
D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D045744:Cell Line, Tumor / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects*; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D019008:Drug Resistance, Neoplasm / Q000528:radiation effects*; D005720:Gamma Rays / Q000627:therapeutic use; D006801:Humans; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D002945:Cisplatin