IL-6 and PPARgamma signalling in human PC-3 prostate cancer cells

Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands and interleukin (IL)-6 are key factors for controlling prostate cancer cell proliferation and survival.

Herein we used the natural PPARgamma ligand, 15deoxy Delta12-14 PGJ(2) (15dPGJ(2)), 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.

15dPGJ(2) reduced PC-3 cell proliferation, while IL-6 increased it. IL-6 induced PPARgamma expression but did not affect the PPARgamma ligand-mediated effects on the proliferation of PC-3 cells. However, 15dPGJ(2) inhibited the IL-6-mediated increase of PC-3 cell proliferation. 15dPGJ(2) 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 15dPGJ(2)-mediated activation of Erk1/2 phosphorylation in PC-3 cells.

The interplay between PPARgamma ligands and IL-6 signalling could be important in controlling the growth of androgen independent prostate cancer cells as exemplified by PC-3 cells.