PPARγ activator rosiglitazone inhibits cell migration via upregulation of PTEN in human hepatocarcinoma cell line BEL-7404

Abstract

PPARγ agonists were reported to be implicated in many biological functions in certain kinds of cells, however, little is known about the effects of PPARγ on hepatocarcinoma cell. We explored the effects of rosiglitazone, a PPARγ activator, on human hepatocarcinoma cell line BEL-7404 and its mechanism. After BEL-7404 was exposed to rosiglitazone, its migration was significantly inhibited, which associated with down-regulation of the phosphorylation of Akt and FAK, while no significant change was detected in the phosphorylation of ERK after rosiglitazone treatment. It is now known that phosphorylated FAK is a substrate of PTEN and Akt phosphorylation can be regulated by PTEN via the PIP₃ level. We found rosiglitazone up-regulated PTEN expression in a dose- and time-dependent manner, which was mediated by PPARγ. Furthermore, PTEN overexpression resulted in inhibition of cell migration and PTEN knock-down blocked the effect of rosiglitazone on cell migration. It suggested that PTEN was required for rosiglitazone-induced inhibition of BEL-7404 cells migration. In conclusion, our results demonstrated that PTEN played a critical role in rosiglitazone inhibiting cell migration in BEL-7404.