Multiple myeloma cells undergo differentiation upon exposure to rosiglitazone and all-trans retinoic acid.
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.
Huang
Haiwen
H
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.
Wu
Depei
D
Fu
Jinxiang
J
Chen
Guanghua
G
D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000032:analysis; D039482:Integrin alpha5 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D000077154:Rosiglitazone; D053668:Syndecan-1 / Q000032:analysis; D045162:Thiazolidinediones / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007147:Immunoglobulin Light Chains; D039482:Integrin alpha5; D047495:PPAR gamma; C508241:SDC1 protein, human; D053668:Syndecan-1; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D014212:Tretinoin