Upregulation of PTEN involved in rosiglitazone-induced apoptosis in human hepatocellular carcinoma cells

Abstract

Aim: To investigate the effects of rosiglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, on the expression of the phosphatase and tensin homologue deleted on chromosome 10 gene (PTEN) and cell growth in hepatocellular carcinoma cells, as well as the underlying mechanisms of these effects. Methods: RT-PCR and Western blotting analyses were performed to detect transcription and the expression of PTEN in Hep3B cells treated with rosiglitazone. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was used to evaluate cell growth. Flow cytometry, DNA fragmentation analysis, caspase enzymatic assay, and Hoechst 33258 staining were used to determine cell apoptosis. Furthermore, small interfering RNA was used to suppress PTEN expression. Results: Rosiglitazone increased the expression of PTEN in a doseand time-dependent manner through the PPARγ-dependent signal transduction pathway. PTEN upregulation was concomitant with a decreased level of Akt phosphorylation, subsequently resulting in cell growth inhibition and apoptosis in Hep3B cells. PTEN knockdown dramatically blocked these effects of rosiglitazone. Moreover, the exposure of cells to rosiglitazone activated caspases-9 and -3 during apoptotic proceeding. Conclusion: Thus, upregulation of PTEN is involved in the inhibition of cell growth and the induction of cell apoptosis by rosiglitazone, suggesting that rosiglitazone may be useful in liver cancer therapy via apoptosis.

Exosome miR-371b-5p promotes proliferation of lung alveolar progenitor type II cells by using PTEN to orchestrate the PI3K/Akt signaling

“…These data demonstrate that miR-371b-5p regulates PTEN expression post-transcriptionally by directly targeting its 3′UTR. We further used the PPARγ agonist Rosiglitazone, which can activate PTEN expression transcriptionally [38, 39], to treat hiPSC-ATIICs for 24 hours after transfection with miR-371b-5p mimic. As mRNA of PTEN can be significantly induced by Rosiglitazone in a dose-dependent manner (data not shown), Rosiglitazone is able to compete the miR-371b-5p mimic-mediated degradation of PTEN mRNA in hiPSC-ATIICs.…”

Rosiglitazone sensitizes hepatocellular carcinoma cell lines to 5-fluorouracil antitumor activity through activation of the PPARγ signaling pathway

“…PPARγ is a nuclear receptor with multiple biologic effects. Recent evidence has demonstrated that PPARγ activation by TZDs inhibits cell growth and induces cell apoptosis in liver cancer cell lines [24,25] . Moreover, rosiglitazone, as a PPARγ synthetic ligand, has been shown to enhance the antitumor www.chinaphar.com Cao LQ et al Acta Pharmacologica Sinica npg activity of some chemotherapeautic drugs by the modulation of cancer cell agents [26,27] .…”

Knockdown of FoxM1 by siRNA interference decreases cell proliferation, induces cell cycle arrest and inhibits cell invasion in MHCC-97H cells in vitro

“…Most HCC cases occur in either Eastern Asia, especially in China, or sub-Saharan Africa [1] . Currently, the prognosis for HCC is still poor, as no effective therapy has been developed [2] . Gene targeting is a relatively new approach to cancer therapy, and a key requirement of gene targeting therapy is to have specific and efficient targets.…”