15-Deoxy-Δ12,14-prostaglandin J2 Inhibits Cell Migration on Renal Cell Carcinoma via Down-Regulation of Focal Adhesion Kinase Signaling

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-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is an endogenous anti-cancerous agent. Treatment with high concentrations of 15d-PGJ(2) is known to induce apoptosis of RCC cells, independent of the nuclear receptor, peroxisome proliferator-activated receptor-gamma (PPAR gamma). In this study, we investigated the effects of 15d-PGJ(2) 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-PGJ(2) did not cause apoptosis, it did decrease the migration of Caki-2 cells in a concentration-dependent manner. PPAR gamma did not mediate the inhibitory effect of 15d-PGJ(2) on the migration of Caki-2 cells. Treatment with a low concentration of 15d-PGJ(2) resulted in disassembled focal adhesions and extensive filamentous actin reorganization. Furthermore, 15d-PGJ(2) significantly reduced phosphorylation of focal adhesion kinase (FAK). In conclusion, 15d-PGJ(2) attenuated the migratory ability of RCC, independent of PPAR gamma. Further, 15d-PGJ(2) appeared to suppress cell migration via inactivation of FAK and subsequent disassembly of focal adhesion. Our present study highlights the therapeutic potential of 15d-PGJ(2) for prevention of RCC metastasis.