Glucocorticoid receptors and growth inhibitory effects of dexamethasone in human lung cancer cell lines.
Expression of glucocorticoid receptors (GR) and growth effects of dexamethasone and the antiglucocorticoid RU-486 were investigated in six cell lines originating from small cell lung cancer (SCLC) and 13 cell lines from non-small cell lung cancer (NSCLC; four adenocarcinoma, four squamous cell carcinoma, four large cell carcinoma and one mesothelioma). All cell lines contained specific and saturable binding sites for the synthetic glucocorticoid dexamethasone, as determined by whole cell assays and by cytosolic receptor assays. The presence of GRs in the carcinoma cells was confirmed by immunocytochemistry. In NSCLC cell lines, GRs were present in large amounts (37-638 fmol/mg cytosolic protein). In SCLC cell lines, GRs were also detectable but in considerably lower concentrations. Growth inhibitory effects of dexamethasone were seen in the cultures of two squamous cell carcinoma lines (EPLC-32M1 and NCI-H157), one adenocarcinoma line (A-549), one large cell carcinoma cell line (LCLC-97TM1) and the cell line of a mesothelioma (MSTO-211H). All cell lines responsive to dexamethasone had high GR concentrations (> or = 164 fmol/mg cytosolic protein). The antiglucocorticoid RU-486 was virtually inactive when administered alone but was able to block the growth-inhibitory effect of dexamethasone. The results indicate that glucocorticoids may inhibit the progression of individual non-small cell lung carcinoma.
Hofmann
J
J
Department of Internal Medicine, Philipps-University, Marburg, Germany.
Kaiser
U
U
Maasberg
M
M
Havemann
K
K
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000737:chemistry* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry* / Q000473:pathology; D011965:Receptors, Glucocorticoid / Q000032:analysis*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D018931:Antineoplastic Agents, Hormonal; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone