Treatment of etoposide combined with 15-deoxy-Δ12,14-prostaglandin J2 exerted synergistic antitumor effects against renal cell carcinoma via peroxisome proliferator-activated receptor-γ-independent pathways.

ABSTRACT

Renal cell carcinoma (RCC) is characterized by diverse clinical manifestations, few early warning signs and a resistance to radiotherapy and chemotherapy. Although several clinical trials have investigated potential effective therapeutic strategies for RCC, the chemoresistance of RCC has not yet been overcome. An endogenous ligand for the peroxisome proliferator-activated receptor-γ (PPARγ), 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), was shown to induce apoptosis in RCC. The aim of the present study was to investigate the synergistic effects of carcinostatics on the antitumor activity of 15d-PGJ2 in the Caki-2 human RCC cell line with the MTT assay. Our results demonstrated that the topoisomerase-II inhibitor etoposide (VP-16) exhibited cytotoxic effects synergistically with 15d-PGJ2. Furthermore, the presence of the PPARγ antagonist GW9662 did not protect Caki-2 cells against 15d-PGJ2-induced cytotoxicity. Additionally, it was observed that the combined treatment of VP-16 and 15d-PGJ2 activated caspase-3 more efficiently compared to each treatment alone. Therefore, the combined treatment with 15d-PGJ2 and VP-16 exhibited synergistic antitumor activity independently of PPARγ.