Sequential combinations of flavopiridol and docetaxel inhibit prostate tumors, induce apoptosis, and decrease angiogenesis in the Gγ/T-15 transgenic mouse model of prostate cancer

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Abstract
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 Gγ/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 Gγ/T-15 transgenic mice. An increase in apoptosis and a decrease in angiogenesis resulted in the greatest inhibition of prostate cancers. Prostate 66: 1487–1497, 2006.
Funding Information
  • Sanofi-Aventis Pharmaceuticals (GIA 60025)
  • VA Merit Review (026901)
  • Department of Defense (DAMD17-03-1-0179)