efatutazone and Esophageal-Neoplasms

efatutazone has been researched along with Esophageal-Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for efatutazone and Esophageal-Neoplasms

ArticleYear
Small molecule agonists of PPAR-γ exert therapeutic effects in esophageal cancer.
    Cancer research, 2014, Jan-15, Volume: 74, Issue:2

    The transcription factor PPAR-γ plays various roles in lipid metabolism, inflammation, cellular differentiation, and apoptosis. PPAR-γ agonists used to treat diabetes may have utility in cancer treatment. Efatutazone is a novel later generation PPAR-γ agonist that selectively activates PPAR-γ target genes and has antiproliferative effects in a range of malignancies. In this study, we investigated PPAR-γ status in esophageal squamous cell carcinoma (ESCC) and investigated the antiproliferative effects of efatutazone. PPAR-γ was expressed heterogeneously in ESCC, in which it exhibited an inverse relationship with Ki-67 expression. PPAR-γ expression was associated independently with good prognosis in ESCC. Efatutazone, but not the conventional PPAR-γ agonist troglitazone, inhibited ESCC cell proliferation in vitro and in vivo. Mechanistic investigations suggested that efatutazone acted by upregulating p21Cip1 protein in the nucleus through inactivation of the Akt pathway and dephosphorylation of p21Cip1 at Thr145 without affecting the transcriptional activity of p21Cip1. We also found that treatment with efatutazone led to phosphorylation of the EGF receptor and activation of the mitogen-activated protein kinase (MAPK) pathway. Accordingly, the combination of efatutazone with the antiepithelial growth factor receptor antibody cetuximab synergized to negatively regulate the phosphoinositide 3-kinase-Akt and MAPK pathways. Together, our results suggest that efatutazone, alone or in combination with cetuximab, may offer therapeutic effects in ESCC.

    Topics: Aged; Animals; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Nucleus; Cell Proliferation; Cetuximab; Cyclin-Dependent Kinase Inhibitor p21; Epithelium; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Gene Expression Regulation, Neoplastic; Humans; Male; MAP Kinase Signaling System; Mice; Mice, Nude; Middle Aged; Neoplasm Transplantation; PPAR gamma; Prognosis; Signal Transduction; Thiazolidinediones; Treatment Outcome

2014