Zoledronic acid effects interleukin-6 expression in hormone-independent prostate cancer cell lines.
OBJECTIVE
To investigate the inhibitory effects of zoledronic acid (ZA) on tumor related growth factor IL-6 in hormone resistant prostate cancer cell lines. The association between apoptosis and IL-6 inhibition was also assessed.


METHODS
PC-3 and DU145 cell lines were treated with different concentrations of ZA (1-100 microM) at various intervals (24-72 h.). The cell viability was investigated by XTT assay and apoptotic effect was evaluated by cell death detection ELISA kit. Caspase 3/7 activity assay was performed to confirm apoptosis. IL-6 levels were measured by ELISA in the supernatant, and these data were also confirmed by IL-6 mRNA analysis using RT-PCR.


RESULTS
PC-3 and DU145 cell lines were sensitive to ZA mediated cytotoxicity in a dose- and time-dependent manner. However, the apoptotic effect was significantly different among PC-3 and DU145 cells (p<0.05). IL-6 secretion was significantly lower in both cell lines, compared to the untreated control cells (p<0.05). Although the increased inhibition of IL-6 secretion was associated with increased apoptosis in DU145 cells (p=0.002), there was no similar association for PC-3 cell line (p=0.347). When compared to the untreated controls, the number of cDNA copies was significantly lower in the ZA treated DU145 cell line at doses of 30 and 90 microM (p<0.05), suggesting a reduced expression of IL-6 mRNA.


CONCLUSIONS
ZA exhibited a time- and dose-dependent apoptotic effect on PC-3 and DU145 prostate cancer cell lines and this effect was associated with inhibited secretion of IL-6 in DU145 cell line.
Asbagh
Layka A
LA
Department of Molecular Biology, Faculty of Science and Arts, Celal Bayar University, Manisa, Turkey.
Uzunoglu
Selim
S
Cal
Cag
C
D017209:Apoptosis / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D000077211:Zoledronic Acid; D000093242:Interleukin-6 Inhibitors
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D015850:Interleukin-6; D000077211:Zoledronic Acid; D000093242:Interleukin-6 Inhibitors