Down-regulation of collagen XVIII expression by thiazolidinediones through a PPARγ-dependent mechanism in human non-small lung cancer cells

Thiazolidinedione (TZD) use in patients with diabetes was specifically associated with reduced risk of lung cancer. Since collagen XVIII is one of the strongest predictors of outcome in patients with lung cancer, we examined the effects of TZD on expression of collagen XVIII in human non-small lung cancer (NSCLC) cells to clarify the mechanism by which TZD improves clinical outcome. Troglitazone or ciglitazone inhibited cell growth in cultured NSCLC cell lines, PC-14 and RERF-LC-AI, in dose- and time-dependent manners. The TZDs significantly down-regulated mRNA expression of collagen XVIII as well as cyclin B1, cyclin E2 and survivin in both cell lines. GW9662, a PPARγ antagonist, completely blocked the troglitazone-induced inhibition of collagen XVIII expression. These results suggest for the first time that TZDs reduced expression of collagen XVIII through a PPARγ-dependent mechanism in NSCLC, which may help us understand the mechanism why TZDs use has chemopreventive action.