title: Dexamethasone-induced cisplatin and gemcitabine resistance in lung carcinoma samples treated ex vivo.
abstract: Chemotherapy for lung cancer not only has severe side effects but frequently also exhibits limited, if any clinical effectiveness. Dexamethasone (DEX) and similar glucocorticoids (GCs) such as prednisone are often used in the clinical setting, for example, as cotreatment to prevent nausea and other symptoms. Clinical trials evaluating the impact of GCs on tumour control and patient survival of lung carcinoma have never been performed. Therefore, we isolated cancer cells from resected lung tumour specimens and treated them with cisplatin in the presence or absence of DEX. Cell number of viable and dead cells was evaluated by trypan blue exclusion and viability was measured by the MTT-assay. We found that DEX induced resistance toward cisplatin in all of 10 examined tumour samples. Similar results were found using gemcitabine as cytotoxic drug. Survival of drug-treated lung carcinoma cells in the presence of DEX was longlasting as examined 2 and 3 weeks after cisplatin treatment of a lung carcinoma cell line. These data corroborate recent in vitro and in vivo xenograft findings and rise additional concerns about the widespread combined use of DEX with antineoplastic drugs in the clinical management of patients with lung cancer.
authors.affiliation: Department of Pathology, University of Heidelberg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Gassler
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.forename: T
authors.initials: T
authors.lastname: Wenger
authors.forename: P A
authors.initials: PA
authors.lastname: Schnabel
authors.forename: H
authors.initials: H
authors.lastname: Dienemann
authors.forename: K-M
authors.initials: KM
authors.lastname: Debatin
authors.forename: J
authors.initials: J
authors.lastname: Mattern
authors.forename: I
authors.initials: I
authors.lastname: Herr
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D003907:Dexamethasone; D002945:Cisplatin; D000093542:Gemcitabine