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Inhibition of Lymphoma Cell Proliferation by Peroxisomal Proliferator-Activated Receptor-γ Ligands via Wnt Signaling Pathway

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Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in regulating energy balance, glucose and lipid metabolisms and inflammation. PPARγ also exerts multiple anti-cancer effects including tumor growth and angiogenesis inhibition, induction of cell differentiation, and apoptosis. Perturbed Wnt/β-catenin signaling likely plays a key role in tumorigenesis and the interaction between PPARγ and the transcriptional regulator β-catenin maybe important in this process. Phosphorylation of β-catenin by GSK-3β inactivates it and suppresses tumor cell proliferation and self-renewal of tumor stem cells. In combination with Frizzled, Wnt suppresses GSK-3β and causes degradation of β-catenin and activation of many tumor proliferation factors. In the present study, we investigated the effects of PPARγ agonist rosiglitazone (RGZ) and PPARγ antagonist GW9662 on the growth, mitotic cycle, and apoptosis of human lymphoma cell line, Raji cells. We also studied the influence of PPARγ ligands on the expression of β-catenin and GSK-3β in Raji cells to reveal whether Wnt/GSK-3β/β-catenin signaling pathways are involved in PPARγ ligands triggered Raji cell apoptosis. Results showed that both RGZ and GW9662 can inhibit the growth of Raji cells by inducing apoptosis and arresting cell cycle; however, there was no correlation between these effects and expression of PPARγ. Both the PPARγ ligands, RGZ and GW9662, appear to reciprocally regulate the mRNA and protein expressions of GSK-3β, which promotes apoptosis, and of β-catenin, which blocks apoptosis. These results suggest that PPARγ ligands mediate their effects via Wnt/GSK-3β/β-catenin signaling on Raji cell proliferation and survival.

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Authors and Affiliations

  1. Department of Hematology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, Guangdong, China

    Jia-Jun Liu, Yan Xu, Xiao-Dan Liu, Zhi-Gang Fang, Dong-Jun Lin, Ruo-Zhi Xiao & Ren-Wei Huang

  2. Department of of Neurosurgery, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, 510010, Guangdong, China

    Xue-Jun Dai

  3. Lab of Pharmacology and Toxicology, School of Pharmaceutical Science of Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China

    Pei-Qing Liu & He-Qing Huang

  4. Department of Nuclear Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, Guangdong, China

    Yong Zhang

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  1. Jia-Jun Liu
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Correspondence to Jia-Jun Liu or Yong Zhang.

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Jia-Jun Liu, Xue-Jun Dai, and Yan Xu contributed equally to this study.

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Liu, JJ., Dai, XJ., Xu, Y. et al. Inhibition of Lymphoma Cell Proliferation by Peroxisomal Proliferator-Activated Receptor-γ Ligands via Wnt Signaling Pathway. Cell Biochem Biophys 62, 19–27 (2012). https://doi.org/10.1007/s12013-011-9253-x

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