Peroxisome proliferator-activated receptor δ confers resistance to peroxisome proliferator-activated receptor γ-induced apoptosis in colorectal cancer cells

摘要

Peroxisome proliferator-activated receptor 纬 (PPAR纬) may serve as a useful target for drug development in non-diabetic diseases. However, some colorectal cancer cells are resistant to PPAR纬 agonists by mechanisms that are poorly understood. Here, we provide the first evidence that elevated PPAR未 expression and/or activation of PPAR未 antagonize the ability of PPAR纬 to induce colorectal carcinoma cell death. More importantly, the opposing effects of PPAR未 and PPAR纬 in regulating programmed cell death are mediated by survivin and caspase-3. We found that activation of PPAR纬 results in decreased survivin expression and increased caspase-3 activity, whereas activation of PPAR未 counteracts these effects. Our findings suggest that PPAR未 and PPAR纬 coordinately regulate cancer cell fate by controlling the balance between the cell death and survival and demonstrate that inhibition of PPAR未 can reprogram PPAR纬 ligand-resistant cells to respond to PPAR纬 agonists.