15-Deoxy-Δ12,14-prostaglandin J2 inhibits cell migration on renal cell carcinoma via down-regulation of focal adhesion kinase signaling

Abstract

Renal cell carcinoma (RCC) is one of the chemoresistant cancers. There is a pressing need to establish therapeutic approaches to prevent RCC proliferation and metastasis. The electrophilic 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is an endogenous anti-cancerous agent. Treatment with high concentrations of 15d-PGJ2 is known to induce apoptosis of RCC cells, independent of the nuclear receptor, peroxisome proliferator-activated receptor-γ (PPARγ). In this study, we investigated the effects of 15d-PGJ2 on the metastatic properties of RCC Caki-2 cells. The metastatic potential of RCC was evaluated by measuring the migratory ability of Caki-2 cells. Although treatment with low concentrations of 15d-PGJ2 did not cause apoptosis, it did decrease the migration of Caki-2 cells in a concentration-dependent manner. PPARγ did not mediate the inhibitory effect of 15d-PGJ2 on the migration of Caki-2 cells. Treatment with a low concentration of 15d-PGJ2 resulted in disassembled focal adhesions and extensive filamentous actin reorganization. Furthermore, 15d-PGJ2 significantly reduced phosphorylation of focal adhesion kinase (FAK). In conclusion, 15d-PGJ2 attenuated the migratory ability of RCC, independent of PPARγ. Further, 15d-PGJ2 appeared to suppress cell migration via inactivation of FAK and subsequent disassembly of focal adhesion. Our present study highlights the therapeutic potential of 15d-PGJ2 for prevention of RCC metastasis.