Background: Interleukin-6 (IL-6) is a multifunctional regulator of cellular events in prostate cancer. LNCaP-IL-6+ cells selected in the presence of IL-6 were taken for assessment of effects of the chimeric monoclonal anti-IL-6 antibody CNTO 328.
Methods: Cell viability was assessed after treatment with CNTO 328 by the ATP assay. Expression of Bcl-2 and Bax and activation of signaling pathways were evaluated by Western analysis. Nude mice were inoculated with LNCaP-IL-6+ cells and treated with CNTO 328. The tumors were analyzed by immunohistochemistry for expression of Ki-67, tissue transglutaminase, and vascular endothelial growth factor.
Results: CNTO 328 caused a statistically significant inhibition of cell viability. The protein levels of Bcl-2 and the phosphorylation of ERK1/2 mitogen-activated protein kinases were decreased by the anti-IL-6 antibody. Treatment with CNTO 328 yielded an increase in the phosphorylation of signal transducers and activators of transcription factor 3. The mean tumor volume in animals inoculated with LNCaP-IL-6+ cells and treated with CNTO 328 was insignificantly lower than that in animals treated with the control antibody. There was a statistically significant decrease in the percentage of Ki-67-positive cells in CNTO 328-treated tumors.
Conclusion: CNTO 328 has a potential in prostate cancer therapy and could be further tested in various combination experimental treatments.