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

✍ Scribed by Satish Batra; Richard Karlsson; Lisbeth Witt

Publisher
John Wiley and Sons
Year
1996
Tongue
French
Weight
625 KB
Volume
68
Category
Article
ISSN
0020-7136

No coin nor oath required. For personal study only.

✦ Synopsis

The effects of combining estramustine (EM) with vinblastine (VLB) or doxorubicin (DOX) on cellular uptake, cellular retention and cell survival were investigated in Dunning horrnoneinsensitive rat prostate AT-I tumor cells and DU-145 human prostatic tumor cells. Accumulation of VLB and DOX by AT-I 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-I cells but not in DU-I45 cells. Verapamil and tamoxifen also potentiated VLB uptake in AT-I 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-I cells could be demonstrated by both Western blots and immunocytochemical detection. Photoaffinity labeling of Pgp by pH]-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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