Dexamethasone-induced enhancement of resistance to ionizing radiation and chemotherapeutic agents in human tumor cells.
BACKGROUND
Dexamethasone-induced changes in radioresistance have previously been observed by several authors. Here, we examined effects of dexamethasone on resistance to ionizing radiation in 10 additional human cell lines and strains, and on resistance to carboplatin and paclitaxel in 13 fresh tumor samples.


METHODS
Eight human carcinoma cell lines, a glioblastoma cell line and a strain of normal human diploid fibroblasts were arbitrarily chosen for these in-vitro studies. Effects on radiosensitivity were assessed using a conventional colony formation assay. Effects on resistance to the drugs were investigated prospectively (ATP cell viability assay) using 13 fresh tumor samples from consecutive patients operated for ovarian cancer within the context of a Swiss nation-wide randomized prospective clinical trial (SAKK 45/94).


RESULTS
Dexamethasone promoted proliferation of 1 of the cell lines without affecting radiosensitivity, while it completely inhibited proliferation of 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 no effect on growth or radioresistance, nor in the fibroblasts. Treatment with dexamethasone enhanced resistance of the malignant cells to carboplatin in 4 of the 13 fresh tumor samples examined, while no enhancement in resistance to paclitaxel was observed.


CONCLUSIONS
In agreement with previous reports, we found that dexamethasone may induce radioresistance in human carcinoma cells. Including the published data from the literature, dexamethasone induced enhancement in radioresistance in 4 of 12 carcinoma cell lines (33%), but not in 3 glioblastoma cell lines, nor in 3 fibroblast strains. Dexamethasone also induced enhanced resistance to carboplatin with a similar probability in fresh samples of ovarian cancer evaluated prospectively (in 4 of 13 samples; 31%). We worry that 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 fraction of patients with a carcinoma.
Mariotta
M
M
Laboratoire de Radiobiologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
Perewusnyk
G
G
Koechli
O R
OR
Little
J B
JB
von Knebel Doeberitz
M
M
Mirimanoff
R O
RO
Rutz
H P
HP
D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors*; D000972:Antineoplastic Agents, Phytogenic / Q000037:antagonists & inhibitors; D016190:Carboplatin / Q000037:antagonists & inhibitors; D002478:Cells, Cultured / Q000528:radiation effects; D003907:Dexamethasone / Q000009:adverse effects*; D004307:Dose-Response Relationship, Radiation; D019008:Drug Resistance, Neoplasm / Q000528:radiation effects*; D005260:Female; D005347:Fibroblasts / Q000528:radiation effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D010051:Ovarian Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000037:antagonists & inhibitors; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D014407:Tumor Cells, Cultured / Q000528:radiation effects
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D003907:Dexamethasone; D016190:Carboplatin; D017239:Paclitaxel