首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Human multiple myeloma cells express peroxisome proliferator-activated receptor gamma and undergo apoptosis upon exposure to PPARgamma ligands.
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Human multiple myeloma cells express peroxisome proliferator-activated receptor gamma and undergo apoptosis upon exposure to PPARgamma ligands.

机译:人多发性骨髓瘤细胞表达过氧化物酶体增殖物激活的受体γ,并在暴露于PPARγ配体后发生凋亡。

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摘要

Multiple myeloma is essentially an incurable malignancy and it is therefore of great interest to develop new therapeutic approaches. We previously reported that human B cell-lymphomas express the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) and are killed by PPARgamma ligands. Herein, we investigate the therapeutic potential of PPARgamma ligands for multiple myeloma. The human multiple myeloma cell lines ANBL6 and 8226 express PPARgamma mRNA and protein. The PPARgamma ligands, 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and ciglitazone, induced multiple myeloma cell apoptosis as determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, loss of mitochondrial membrane potential, and caspase activation. Importantly, the ability of PPARgamma ligands to kill both multiple myeloma cell lines was not abrogated by Interleukin-6 (IL-6), a multiple myeloma growth survival factor. Finally, the RXR ligand 9-cis retinoic acid(9-cis RA) in combination with PPARgamma ligands greatly enhanced multiple myeloma cell killing. These new findings support that PPARgamma ligands may represent a novel therapy for multiple myeloma.
机译:多发性骨髓瘤本质上是不能治愈的恶性肿瘤,因此开发新的治疗方法引起了极大的兴趣。我们先前曾报道人类B细胞淋巴瘤表达核受体过氧化物酶体增殖物激活的受体伽玛(PPARgamma),并被PPARgamma配体杀死。本文中,我们研究了PPARgamma配体对多发性骨髓瘤的治疗潜力。人多发性骨髓瘤细胞系ANBL6和8226表达PPARgamma mRNA和蛋白。 PPARgamma配体,15-deoxy-Delta(12,14)-前列腺素J(2)(15d-PGJ(2))和西格列酮诱导多发性骨髓瘤细胞凋亡,如通过末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记所确定的(TUNEL)分析,线粒体膜电位损失和半胱天冬酶激活。重要的是,白介素6(IL-6)(一种多发性骨髓瘤生长生存因子)并未消除PPARγ配体杀死两种多发性骨髓瘤细胞系的能力。最后,RXR配体9-顺式视黄酸(9-顺式RA)与PPARγ配体的结合大大增强了多发性骨髓瘤细胞的杀伤力。这些新发现支持PPARgamma配体可能代表多发性骨髓瘤的一种新颖疗法。

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