15-Deoxy-Δ12,14-prostaglandin J2 enhances docetaxel anti-tumor activity against A549 and H460 non-small-cell lung cancer cell lines and xenograft tumors

15-Deoxy-Δ-prostaglandin J2 is a naturally occurring endogenous ligand for peroxisome proliferator-activated receptor-γ. The current study was aimed to determine the mechanism of anti-proliferative effect of 15-deoxy-Δ-prostaglandin J2+docetaxel against A549 and H460 non-small-cell lung cancer cell lines and xenograft tumors. In-vitro cytotoxicity of 15-deoxy-Δ-prostaglandin J2 alone and in combination with docetaxel was studied against A549 and H460 cell lines. For in-vivo studies, female athymic nu/nu mice were xenografted with A549 and H460 tumors and treated with 15-deoxy-Δ-prostaglandin J2 (1 mg/kg/day; intraperitoneal), docetaxel (10 mg/kg; intravenous on days 14, 18 and 22) and 15-deoxy-Δ-prostaglandin J2+docetaxel. Apoptosis was measured in A549 cells and tumor tissues, following various treatments. Peroxisome proliferator-activated receptor-γ, caspases, Bcl2 and p53 family proteins or their mRNA expressions were measured by Western blotting, reverse transcription-polymerase chain reaction and real-time polymerase chain reaction in A549 tumors. A possible role of a peroxisome proliferator-activated receptor-γ-independent mechanism was studied in A549 cells treated with peroxisome proliferator-activated receptor-γ antagonist, GW9662. Isobolographic analysis demonstrated synergistic interaction (combination index