Huang Haiwen, Wu Depei, Fu Jinxiang, Chen Guanghua
Department of Hematology, the First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thombosis and Hemostasis, Ministry of Health, Suzhou, China.
Leuk Lymphoma. 2009 Jun;50(6):966-73. doi: 10.1080/10428190902866724.
Activation of PPARgamma by its ligands has shown differentiating effects in solid tumors. However, few reports addressed its role in myeloma cells. Our study demonstrated that exposure to PPARgamma ligand (rosiglitazone, RGZ) induced proliferation inhibition and cell cycle arrest in myeloma cells. A combination of RGZ with all-trans retinoic acid (ATRA) can enhance the growth inhibition effects of RGZ. Further study shows that RGZ-treated myeloma cells displayed morphological characteristics of cell differentiation, and more evident signs of differentiation were observed when RGZ was combined with ATRA. These changes were confirmed by the detection of CD49e expression and light chain protein secretion. Similar results were also observed when primary CD138(+) cells were treated with RGZ and ATRA. Collectively, our study revealed that RGZ can induce cell differentiation in myeloma cells and concomitant treatment with ATRA can enhanced the effects of RGZ.
其配体对过氧化物酶体增殖物激活受体γ（PPARγ）的激活在实体瘤中已显示出分化作用。然而，很少有报告涉及其在骨髓瘤细胞中的作用。我们的研究表明，暴露于PPARγ配体（罗格列酮，RGZ）可诱导骨髓瘤细胞增殖抑制和细胞周期停滞。RGZ与全反式维甲酸（ATRA）联合使用可增强RGZ的生长抑制作用。进一步研究表明，经RGZ处理的骨髓瘤细胞表现出细胞分化的形态学特征，当RGZ与ATRA联合使用时，观察到更明显的分化迹象。通过检测CD49e表达和轻链蛋白分泌证实了这些变化。当用RGZ和ATRA处理原代CD138(+)细胞时，也观察到了类似结果。总体而言，我们的研究表明，RGZ可诱导骨髓瘤细胞分化，与ATRA联合治疗可增强RGZ的作用。
