Abstract
Background: Peroxisome proliferator-activated receptor gamma (PPARγ) ligands and interleukin (IL)-6 are key factors for controlling prostate cancer cell proliferation and survival. Materials and Methods: Herein we used the natural PPARγ ligand, 15deoxy Δ12-14 PGJ2 (15dPGJ2), and IL-6 to define their interactions on proliferation and signal transduction in PC-3 cells. Cytotoxic and trypan blue exclusion assays, Western blot analysis of mitogen-activated protein kinases (MAPK) and Janus kinase/Signal transducer and activator of transcription (JAK/Stat) and real-time polymerase chain reaction (PCR) were methods employed as investigation tools. Results: 15dPGJ2 reduced PC-3 cell proliferation, while IL-6 increased it. IL-6 induced PPARγ expression but did not affect the PPARγ ligand-mediated effects on the proliferation of PC-3 cells. However, 15dPGJ2 inhibited the IL-6-mediated increase of PC-3 cell proliferation. 15dPGJ2 activated Erk1/2 phosphorylation without affecting Akt phosphorylation and reduced phosphorylated and unphosphorylated Stat3 in PC-3 cells. IL-6 suppressed endogenous activation of Stat3 without affecting Erk1/2 and Akt phosphorylation and suppressed the 15dPGJ2-mediated activation of Erk1/2 phosphorylation in PC-3 cells. Conclusion: The interplay between PPARγ ligands and IL-6 signalling could be important in controlling the growth of androgen independent prostate cancer cells as exemplified by PC-3 cells.
Footnotes
- Received September 23, 2008.
- Revision received November 25, 2008.
- Accepted March 11, 2009.
- Copyright© 2009 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved