Regulation of growth of prostate cancer cells selected in the presence of interleukin-6 by the anti-interleukin-6 antibody CNTO 328.
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.


CONCLUSIONS
CNTO 328 has a potential in prostate cancer therapy and could be further tested in various combination experimental treatments.
Steiner
Hannes
H
Department of Urology, Innsbruck Medical University, Innsbruck, Austria.
Cavarretta
Ilaria T
IT
Moser
Patrizia L
PL
Berger
Andreas P
AP
Bektic
Jasmin
J
Dietrich
Hermann
H
Zaki
Mohamed H
MH
Nakada
Marian
M
Hobisch
Alfred
A
Nemeth
Jeffrey A
JA
Culig
Zoran
Z
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology*; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D050796:STAT3 Transcription Factor / Q000378:metabolism; D011503:Transglutaminases / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D019394:Ki-67 Antigen; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; D011503:Transglutaminases; D042461:Vascular Endothelial Growth Factor A; D000093242:Interleukin-6 Inhibitors; C494086:STAT3 protein, human