Anti‐proliferative effect of rosiglitazone in the human T‐lymphocyte leukaemia cell line Jurkat cells

Abstract Peroxisome proliferator‐activated receptor γ (PPARγ) is expressed in various types of human cancer cells including leukaemia cells, and activation of PPARγ can inhibit cancer cell growth. However, whether PPARγ is expressed in Jurkat cells, a human T‐lymphocyte leukaemia cell line, and whether activation of PPARγ affects cell biological behaviors remains to be clarified. In this study, we investigated the effect of a PPARγ activator rosiglitazone, under clinically relevant pharmacological concentrations, on the growth and apoptosis of Jurkat cells in vitro and explored the possible mechanism. Metformin was also included as a positive control for the anti‐proliferative and pro‐apoptotic effects. We found that PPARγ mRNA was transcribed in Jurkat cells. Treatment with rosiglitazone (5 µM, 10 µM, and 20 µM) or metformin (1 mM and 10 mM) inhibited cell proliferation, and induced cell cycle arrest at G0/G1 or S phase, respectively, in a dose‐dependent manner. Although metformin significantly upregulated the protein levels of the pro‐apoptotic markers cleaved‐caspase 3 and Bax in Jurkat cells, rosiglitazone did not have such an effect. Moreover, rosiglitazone significantly upregulated the level of PPARγ, and downregulated the expression of insulin receptor (IR) and insulin‐like growth factor 1 receptor (IGF‐1R) in a dose‐dependent manner. Our data indicate that rosiglitazone has an anti‐proliferative effect in Jurkat cells, which may be at least partly mediated via downregulating IR and IGF‐1R expression. Therefore, rosiglitazone may have a potential role not only for management of hyperglycaemia but also for control of tumor progression in patients with T‐lymphocyte leukaemia and diabetes.