Additive/synergistic antitumoral effects on prostate cancer cells in vitro following treatment with a combination of docetaxel and zoledronic acid.
Once bone metastasized and androgen independent, prostate cancer is often associated with skeletal morbidity and disability. New treatment modalities that can palliate symptoms from the skeleton and inhibit further progression are warranted. In this study, the antitumoral effects following treatment with a combination of docetaxel and the new generation bisphosphonate, zoledronic acid, were investigated on two hormone-refractory prostate cancer cell lines: PC3 and DU145. The prostate cancer cells were treated with increasing concentrations of zoledronic acid in the absence or presence of docetaxel. Toxicity was measured using fluorometric microculture cytotoxic assay technique. A concentration of 25 microM, zoledronic acid reduced the viable cell number to 68% and 98% for PC3 and DU145 cells respectively. Docetaxel, on the other hand, at a concentration of 0.1 ng/ml, had no effect on the viability. However, a combination of zoledronic acid and docetaxel reduced the cell number to 60% and 81% respectively. Furthermore, zoledronic acid in the concentration range 12.5 microM-50 microM enhanced the antitumoral effects of docetaxel (0.01-1 ng/ml) in an additive and/or synergistic manner for both cell lines. These data support the hypothesis that zoledronic acid, in addition to having bone resorption inhibiting properties, also exhibits anti-tumoral effects. It also appears that combined treatment with docetaxel causes additive and/or synergistic cytostatic effects on prostate cancer cells.
Ullén
Anders
A
Department of Oncology-Pathology Karolinska Institute, Stockholm, Sweden. anders.ullen@karolinska.se
Lennartsson
Lena
L
Harmenberg
Ulrika
U
Hjelm-Eriksson
Marie
M
Kälkner
Karl Mikael
KM
Lennernäs
Bo
B
Nilsson
Sten
S
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001859:Bone Neoplasms / Q000517:prevention & control / Q000556:secondary; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000008:administration & dosage* / Q000494:pharmacology; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008938:Mitosis / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage* / Q000494:pharmacology; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D043823:Taxoids; D000077143:Docetaxel; D000077211:Zoledronic Acid