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 exp lore 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 p rostate cancer cell line that produces IL-6 (PC-3) were established in nude mice. The mice were randomly divided into four treatment groups: (1) salin e (vehicle control) + murine IgG (isotype control); (2) etoposide + murine IgG; (3) saline + anti-IL-6 monoclonal antibody; and (4) etoposide + anti I L-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 a poptosis by TUNEL analysis. RESULTS. Anti-IL-6 Ab (with saline or etoposide) induced tumor apoptosis an d regression (similar to 60% compared to initial tumor size). Etoposide alo ne did not induce tumor regression or apoptosis in this animal model, and t here 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.