Dexamethasone-induced enhancement of resistance to ionizing radiation and chemotherapeutic agents in human tumor cells

Background: Dexamethasone-induced changes in radioresistance have previousl y been observed by several authors. Here, we examined effects of dexamethas one on resistance to ionizing radiation in 10 additional human cell lines a nd strains, and on resistance to carboplatin and paclitaxel in 13 fresh tum or samples. Material and Methods: Eight human carcinoma cell lines, a glioblastoma cell line and a strain of normal human diploid fibroblasts were arbitrarily cho sen for these in-vitro studies. Effects on radiosensitivity were assessed u sing a conventional colony formation assay. Effects on resistance to the dr ugs were investigated prospectively (ATP cell viability assay) using 13 fre sh tumor samples from consecutive patients operated for ovarian cancer with in the context of a Swiss nation-wide randomized prospective clinical trial (SAKK 45/94). Results: Dexamethasone promoted proliferation of 1 of the cell lines withou t affecting radiosensitivity, while it completely inhibited proliferation o f another cell line (effects on radiosensitivity could thus not be examined ). Furthermore, dexamethasone induced enhanced radioresistance in 1 of the 8 carcinoma cell lines examined. In the glioblastoma cell line, there was n o effect on growth or radioresistance, nor in the fibroblasts. Treatment wi th dexamethasone enhanced resistance of the malignant cells to carboplatin in 4 of the 13 fresh tumor samples examined, while no enhancement in resist ance to paclitaxel was observed. Conclusions: In agreement with previous reports, we found that dexamethason e may induce radioresistance in human carcinoma cells. Including the publis hed data from the literature, dexamethasone induced enhancement in radiores istance in 4 of 12 carcinoma cell lines (33%), but not in 3 glioblastoma ce ll lines, nor in 3 fibroblast strains. Dexamethasone also induced enhanced resistance to carboplatin with a similar probability in fresh samples of ov arian cancer evaluated prospectively (in 4 of 13 samples; 31%). We worry th at induction of resistance by corticosteroids given to patients undergoing either radiotherapy or chemotherapy with agents causing DNA damage might be associated with a reduced clinical responsiveness in a significant fractio n of patients with a carcinoma.