Receptor-mediated antiproliferative effects of corticosteroids in Lewis lung tumors.
Dextran-coated charcoal competitive binding assays and Scatchard analysis revealed the presence of high-affinity, low capacity binding sites for dexamethasone in cytosol preparations from Lewis lung tumors. In vitro studies with live cells indicated approximately 9000 nuclear binding sites/cell for the ligand-receptor complex. In vivo inhibition of cell proliferation by dexamethasone, methylprednisolone and triamcinolone acetonide was found to be dose-dependent. Changes in the [3H]-TdR labeling index, mitotic index and saturable cytosol receptor sites after dexamethasone treatment in vivo suggested a dose-dependent G1 progression delay which, after cessation of dexamethasone treatments, was apparently reversible. Resumption of cell-cycle progression was characterized by synchronous progression through S-phase and correlated temporally with receptor site desaturation. In vivo studies indicated that the effectiveness of vincristine given after dexamethasone was highly sequence-dependent, with the most effective sequence interval being coincident with the interval of maximal S-phase cellularity. Other studies indicated sequential chemotherapy with dexamethasone, vincristine and 5-Fu could be effectively employed, following primary tumor excision, to increase animal survival.
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000032:analysis / Q000188:drug therapy*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000032:analysis*; D011987:Receptors, Steroid / Q000032:analysis*; D014222:Triamcinolone Acetonide / Q000627:therapeutic use; D014750:Vincristine / Q000627:therapeutic use
D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; C028697:dexamethasone receptor; D014750:Vincristine; D003907:Dexamethasone; D014222:Triamcinolone Acetonide; D005472:Fluorouracil; D008775:Methylprednisolone