title: Potentiation by estramustine of the cytotoxic effect of vinblastine and doxorubicin in prostatic tumor cells.
abstract: The effects of combining estramustine (EM) with vinblastine (VLB) or doxorubicin (DOX) on cellular uptake, cellular retention and cell survival were investigated in Dunning hormone-insensitive rat prostate AT-1 tumor cells and DU-145 human prostatic tumor cells. Accumulation of VLB and DOX by AT-1 cells was less than one-half of that in DU-145 cells. Inclusion of EM or estromustine considerably increased uptake of both VLB and DOX in AT-1 cells but not in DU-145 cells. Verapamil and tamoxifen also potentiated VLB uptake in AT-1 cells. A combination of VLB and EM resulted in a considerable synergistic effect on both cytotoxicity and cellular retention of VLB. The presence of P-glycoprotein (Pgp) in AT-1 cells could be demonstrated by both Western blots and immunocytochemical detection. Photoaffinity labeling of Pgp by [3H]-azidopine was clearly inhibited by VLB, verapamil and EM. Our data strongly support the argument for a combination of EM with not only VLB but also DOX to improve the therapeutic index in patients with prostate cancer.
authors.affiliation: Pharmacia Oncology Immunology, Lund, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Batra
authors.forename: R
authors.initials: R
authors.lastname: Karlsson
authors.forename: L
authors.initials: L
authors.lastname: Witt
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage; D004357:Drug Synergism; D004961:Estramustine / Q000008:administration & dosage; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D051381:Rats; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D004961:Estramustine; D014747:Vinblastine; D004317:Doxorubicin