Background and aims: We observed a marked synergism between peroxisome proliferator-activated receptor gamma (PPARgamma) ligands and X-linked inhibitor of apoptosis (XIAP) down-regulation in colon cancer. In the current study, we detected the gene expression profile in HCT116 cells treated with or without PPARgamma ligand troglitazone.
Materials and methods: HCT116-XIAP(+/+) and HCT116-XIAP(-/-) cells were treated with or without 50 microM troglitazone for 48 h. Gene expressions were detected by microarray, and selected genes were validated by reverse-transcriptase polymerase chain reaction (PCR), real-time PCR, and Western blot.
Results: Relative to HCT116-XIAP(+/+) cells, 58 genes were up-regulated and 33 genes down-regulated in HCT116-XIAP(-/-) cells, all by > or =4-fold. These genes could be classified into a wide variety of functional classes, but we focused on those related to angiogenesis, apoptosis, and proliferation. Thus, two pro-apoptotic genes and one pro-proliferation gene were up-regulated in HCT116-XIAP(-/-) cells. Two pro-proliferation genes, one pro-angiogenesis gene, one anti-angiogenesis gene, and one anti-apoptosis gene were down-regulated in HCT116-XIAP(-/-) cells. Relative to HCT116-XIAP(+/+) cells treated with troglitazone, 137 genes were up-regulated, and 31 genes were down-regulated in troglitazone-treated HCT116-XIAP(-/-) cells, all by > or =4-fold. Among the up-regulated genes were two anti-angiogenesis genes, seven pro-apoptosis genes, and six anti-proliferation genes. Among the down-regulated genes were one anti-angiogenesis gene, one pro-angiogenesis gene, one anti-apoptosis gene, one anti-proliferation gene, and two pro-proliferation genes.
Conclusion: Down-regulation of XIAP in HCT116 cells with or without troglitazone treatment was associated with changes of gene expression that favor increased tendency of apoptosis, decreased cell proliferation, and angiogenesis potential.