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Updated: Oct 13, 2026
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
Treatment of androgen-independent prostate cancer using antimicrotubule agents docetaxel and estramustine in
J F Williams1, H J Muenchen, J M Kamradt
1Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor 48109-9480, USA.
Background:
Estramustine in combination with other chemotherapeutic agents has demonstrated synergy in hormone-refractory prostate cancer. Docetaxel has demonstrated antineoplastic activity in a variety of chemotherapeutic-unresponsive tumors. We evaluated the effects of estramustine and docetaxel in preclinical models of prostate cancer.
Methods:
Cell viability of PC-3 and MAT-LyLu (MLL) cells were assessed 48 hr after drug treatment. For in vivo studies, each flank of five animals in six groups was injected with 1 x 10(6) MLL cells: control, estramustine, docetaxel (low- and high-dose), and low- and high-dose docetaxel with estramustine. Animals were treated on days 4 and 11, and sacrificed on day 14.
Results:
The IC(50) value for docetaxel was 2 nM in the PC-3 cells and 40 nM in the MLL cells. The addition of 100 nM of estramustine did not alter the IC(50) value for PC-3 cells. In the MLL cells, however, the IC(50) value was lowered to 15 nM. In vivo, low-dose docetaxel with estramustine demonstrated antineoplastic activity similar to that of high-dose docetaxel alone, suggesting additive activity between the drugs.
Conclusions:
These results demonstrate that when used in combination, docetaxel and estramustine can be more effective at lower dosages than when the individual drugs are used alone.
