Alteration of PPAR-GAMMA (PPARG; PPARγ) and PTEN gene expression in acute myeloid leukemia patients and the promising anticancer effects of PPARγ stimulation using pioglitazone on AML cells

Background: In the new era of tailored cancer treatment strategies, finding a molecule to regulate a wide range of intracellular functions is valuable. The unique property of nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR gamma; PPARG) in transmitting the anti-survival signals of the chemotherapeutic drugs has fired the enthusiasm into the application of this receptor in cancer treatment. Objectives: We aimed to investigate the expression of PPAR gamma and one of its downstream targets PTEN in non-M3 acute myeloid leukemia (AML) patients. We also investigated the therapeutic value of PPAR gamma stimulation using pioglitazone in the AML-derived U937 cell line. Methods: The blood samples from 30 patients diagnosed with non-M3 AML as well as 10 healthy individuals were collected and the mRNA expression levels of PPAR gamma and PTEN were evaluated. Additionally, we used trypan blue assay, MTT assay, and flow cytometry analysis to evaluate the anti-leukemic effects of pioglitazone on U937 cells. Results: While PTEN was significantly downregulated in AML patients as compared to the control group, the expression of PPAR gamma was increased in the patients' group. The expression level of PPAR gamma was also negatively correlated with PTEN gamma however, it was not statistically significant. Besides, PPAR gamma stimulation using pioglitazone reduced survival and proliferative capacity of 0937 cells through inducing apoptosis and suppression of cell transition from the G1 phase of the cell cycle. Conclusion: The results of the present study shed more light on the importance of PPAR gamma and its stimulation in the therapeutic strategies of AML.