Corticosteroids induce chemotherapy resistance in the majority of tumour cells from bone, brain, breast, cervix, melanoma and neuroblastoma

Chengwen Zhang, Benjamin Beckermann, Georgios Kallifatidis, Zheng Liu, Werner Rittgen, Lutz Edler, Peter Büchler, Klaus Michael Debatin, Markus W. Büchler, Helmut Friess, Ingrid Herr

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60 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1295-1301
Number of pages7
JournalInternational Journal of Oncology
Volume29
Issue number5
StatePublished - Nov 1 2006
Externally publishedYes

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Keywords

  • Apoptosis
  • Cancer therapy
  • Glucocorticoids
  • Nausea

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Zhang, C., Beckermann, B., Kallifatidis, G., Liu, Z., Rittgen, W., Edler, L., Büchler, P., Debatin, K. M., Büchler, M. W., Friess, H., & Herr, I. (2006). Corticosteroids induce chemotherapy resistance in the majority of tumour cells from bone, brain, breast, cervix, melanoma and neuroblastoma. International Journal of Oncology, 29(5), 1295-1301.