Anti-interleukin-6 monoclonal antibody induces regression of human prostate cancer xenografts in nude mice

BACKGROUND. Despite clinical associations and in vitro data suggesting that autocrine interleukin-6 (IL,-6) production contributes to prostate cancer progression or chemotherapy resistance, there have been no reports that explore the role of Ii,-6 on prostate tumors in vivo. In the present study, we investigated the effect of IL-6 inhibition on the growth of human prostate cancer xenografts in nude mice. METHODS. To determine if autocrine IL,-6 production contributes to prostate cancer growth and chemotherapy resistance in vivo, xenografts of a human prostate cancer cell line that produces IL-6 (PC-3) were established in nude mice. The mice were randomly divided into four treatment groups: (1) saline (vehicle control) + murine IgG (isotype control); (2) etoposide + murine IgG; (3) saline + anti-IL-6 monoclonal antibody; and (4) etoposide + anti IL-6 monoclonal antibody. Tumors were measured twice weekly during a 4-week treatment period. At the conclusion of the study, all mice were sacrificed, and in addition to final volume, tumors were evaluated for the degree of apoptosis by TUNEL analysis. RESULTS. Anti-IL-6 Ab (with saline or etoposide) induced tumor apoptosis and regression (similar to 60% compared to initial tumor size). Etoposide alone did not induce tumor regression or apoptosis in this animal model, and there was no synergy between anti-IL-6 Ab and etoposide. CONCLUSIONS. These studies suggest that IL-6 contributes to prostate cancer growth in vivo, and that targeting IL-6 may contribute to prostate cancer therapy. Prostate 48:47-53, 2001 (C) 2001 Wiley-Liss, Inc.