Sequential combinations of flavopiridol and docetaxel inhibit prostate tumors, induce apoptosis, and decrease angiogenesis in the Ggamma/T-15 transgenic mouse model of prostate cancer.
BACKGROUND
We investigated whether sequential combinations of flavopiridol and docetaxel can increase apoptotic cell death and inhibit the growth of primary and metastatic prostate tumors in the Ggamma/T-15 transgenic mouse model of prostate cancer.


METHODS
Transgenic males were treated and the weights of primary and metastatic prostate tumors determined. Immunohistochemistry and Western blot was performed to evaluate the differences in apoptosis, proliferation, and angiogenesis.


RESULTS
Docetaxel was slightly more effective than flavopiridol in inhibiting primary prostate tumors, but neither drug alone inhibited metastases. Single drug treatments decreased angiogenesis but did not increase apoptosis. Both sequential combinations resulted in greater inhibition of primary and metastatic prostate tumors, increased apoptosis, and decreased angiogenesis compared to control mice.


CONCLUSIONS
Flavopiridol and docetaxel sequence combinations were effective in inhibiting prostate tumors in the Ggamma/T-15 transgenic mice. An increase in apoptosis and a decrease in angiogenesis resulted in the greatest inhibition of prostate cancers.
Reiner
Teresita
T
Department of Medicine and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA.
de las Pozas
Alicia
A
Perez-Stable
Carlos
C
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D000077143:Docetaxel; D004359:Drug Therapy, Combination; D005419:Flavonoids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D010880:Piperidines / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D043823:Taxoids / Q000494:pharmacology*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; C494812:Bcl2l1 protein, mouse; D005419:Flavonoids; D010880:Piperidines; D043823:Taxoids; D051636:X-Linked Inhibitor of Apoptosis Protein; D051020:bcl-X Protein; D000077143:Docetaxel; C077990:alvocidib