Anti-interleukin-6 monoclonal antibody induces regression of human prostate cancer xenografts in nude mice
Article first published online: 31 MAY 2001
Copyright © 2001 Wiley-Liss, Inc.
Volume 48, Issue 1, pages 47–53, 15 June 2001
How to Cite
Smith, P. C. and Keller, E. T. (2001), Anti-interleukin-6 monoclonal antibody induces regression of human prostate cancer xenografts in nude mice. Prostate, 48: 47–53. doi: 10.1002/pros.1080
- Issue published online: 31 MAY 2001
- Article first published online: 31 MAY 2001
- Manuscript Accepted: 2 MAR 2001
- Manuscript Received: 18 DEC 2000
- USAMRMC Prostate Cancer Research Program. Grant Number: DAMD17-00-1-053
- National Institutes of Health. Grant Numbers: T32 RR07008, SPORE 1 P50 CA69568
- prostate cancer;
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 IL-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.
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.
Anti-IL-6 Ab (with saline or etoposide) induced tumor apoptosis and regression (∼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.
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. © 2001 Wiley-Liss, Inc.