Corticosteroids induce chemotherapy resistance in the majority of tumour cells from bone, brain, breast, cervix, melanoma and neuroblastoma.
Glucocorticoids (GCs) such as dexamethasone (DEX) have been widely used as co-medication in cancer therapy because they have potent proapoptotic properties in lymphoid cells, can reduce nausea, and alleviate acute toxic effects in healthy tissue. However, GCs are used in a supportive-care role, even though no prospective clinical studies have assessed the effect of these steroids on the growth of solid tumours. Data from preclinical and, to some extent, clinical studies, suggest that GCs induce treatment resistance in some solid tumours. Since it is unknown whether GC-induced resistance occurs only occasionally or is a more common phenomenon, we performed a screening study using several established cell lines from bone, brain, breast and cervix carcinoma as well as melanoma and neuroblastoma together with fresh surgical resections from patients with breast cancer. We found that DEX inhibits cisplatin and 5-fluorouracil-induced apoptosis and promotes the growth of the majority of examined malignant cells. In contrast, and as expected, DEX acted pro-apoptotically and promoted the cytotoxic effect of chemotherapy in established and primary lymphoid cells. Thus, these data demonstrate the need for detailed molecular studies to clarify the mechanism of differential glucocorticoid signaling as well as controlled, prospective clinical studies.
Zhang
Chengwen
C
Research Group Molecular OncoSurgery, University of Heidelberg, Heidelberg, Germany.
Beckermann
Benjamin
B
Kallifatidis
Georgios
G
Liu
Zheng
Z
Rittgen
Werner
W
Edler
Lutz
L
Büchler
Peter
P
Debatin
Klaus-Michael
KM
Büchler
Markus W
MW
Friess
Helmut
H
Herr
Ingrid
I
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis; D001681:Biological Assay; D001859:Bone Neoplasms / Q000188:drug therapy; D001932:Brain Neoplasms / Q000188:drug therapy; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D003907:Dexamethasone / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy; D009447:Neuroblastoma / Q000188:drug therapy; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
D018931:Antineoplastic Agents, Hormonal; D005938:Glucocorticoids; D003907:Dexamethasone; D002945:Cisplatin; D005472:Fluorouracil