The combinatory effects of PPAR-γ agonist and survivin inhibition on the cancer stem-like phenotype and cell proliferation in bladder cancer cells.

Abstract

Strategies for peroxisome proliferator-activated receptor (PPAR) activation or survivin inhibition have potential for cancer therapy. However, whether the combination of these two approaches can be developed as a rational regimen with enhanced efficiency in the inhibition of tumor cells remains to be determined. In this study, the combinatory effect of PPAR-γ agonist and survivin inhibition on bladder cancer cells was investigated. T24 and 5637 cells were treated with 15d-PGJ(2) to determine whether 15d-PGJ(2) had an inhibitory effect. Cell viability and proliferation were analyzed and efficiency of survivin siRNAs was assessed using western blot analysis. The results showed that, in the human bladder cancer cell lines T24 and 5637, the natural PPAR-γ ligand 15d-PGJ(2) significantly decreased cell proliferation and loci formation. The increase in the proportion of apoptotic cells was observed in the cells 48 h after 15d-PGJ(2) treatment. Furthermore, 15d-PGJ(2) substantially inhibited the levels of stemness-related genes in these cells. The ability of sphere formation was markedly suppressed in the cells treated with 15d-PGJ(2). More importantly, the downregulation of survivin with siRNAs significantly enhanced the 15d-PGJ(2)-mediated induction of cell apoptosis and inhibition of sphere formation. Accordingly, we also found that survivin inhibition significantly enhanced 15d-PGJ(2)-induced production of reactive oxygen species (ROS) in bladder cancer cells. Taken together, these findings suggest that the combination of 15d-PGJ(2) and survivin inhibition play a potentially role in the therapeutical manipulation of bladder cancer.