Docetaxel-induced growth inhibition and apoptosis in androgen independent prostate cancer cells are enhanced by 1alpha,25-dihydroxyvitamin D3.
Pre-treatment with high-dose 1alpha,25-dihydroxyvitamin D(3) (1,25-VD) enhanced the antitumor activity of docetaxel in the androgen-independent prostate cancer cell line, PC-3. The effect manifested as an increasing population of apoptotic cells and amount of pro-apoptotic protein, Bax, under combined treatment compared with single treatment of either 1,25-VD or docetaxel alone. We further demonstrated that pre-treatment with 1,25-VD reduced the expression of multidrug resistance-associated protein-1 at both the mRNA and protein levels. This suggests pre-treatment with 1,25-VD can potentiate cytotoxicity of docetaxel in PC-3 due to 1,25-VD reducing multidrug resistance-associated protein-1 expression.
Ting
Huei-Ju
HJ
Department of Urology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Hsu
Jeffery
J
Bao
Bo-Yin
BY
Lee
Yi-Fen
YF
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000728:Androgens / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D004357:Drug Synergism; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000728:Androgens; C494826:BAX protein, human; D043823:Taxoids; D051028:bcl-2-Associated X Protein; D000077143:Docetaxel; D002117:Calcitriol