Potentiation by estramustine of the cytotoxic effect of vinblastine and doxorubicin in prostatic tumor cells

International Journal of Cancer. Journal International Du Cancer
S BatraL Witt

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.

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Citations

Oct 6, 1997·Proceedings of the National Academy of Sciences of the United States of America·D PandaL Wilson
Apr 14, 2006·Neoplasia : an International Journal for Oncology Research·Oliver ThewsMichael Gekle
Jan 6, 2005·Clinical Oncology : a Journal of the Royal College of Radiologists·S R MuthuramalingamA Protheroe
Jun 18, 2010·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Mirit ArgovRimona Margalit
Jun 6, 2007·Doklady. Biochemistry and Biophysics·E A BogushM I Davydov

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