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Multiple myeloma cells undergo differentiation upon exposure to rosiglitazone and all-trans retinoic acid
Haiwen Huang1, Depei Wu, Jinxiang Fu
1Department of Hematology, the First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thombosis and Hemostasis, Ministry of Health, Suzhou, China.
Abstract:
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.
Insights
Rosiglitazone (RGZ) activates PPARgamma, inhibiting myeloma cell growth and inducing differentiation. Combining RGZ with all-trans retinoic acid (ATRA) enhances these anti-myeloma effects.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands show anti-cancer effects in solid tumors.
- The role of PPARgamma in myeloma cells remains less understood.
Purpose of the Study:
- To investigate the effects of PPARgamma ligand rosiglitazone (RGZ) on myeloma cells.
- To evaluate the combined effects of RGZ and all-trans retinoic acid (ATRA) on myeloma cell growth and differentiation.
Main Methods:
- Myeloma cells were treated with RGZ alone and in combination with ATRA.
- Cell proliferation, cell cycle, morphology, CD49e expression, and light chain secretion were analyzed.
- Primary CD138(+) myeloma cells were also tested.
Main Results:
- RGZ induced proliferation inhibition and cell cycle arrest in myeloma cells.
- RGZ treatment led to morphological differentiation, increased CD49e expression, and reduced light chain secretion.
- Combination therapy with ATRA significantly enhanced RGZ's growth inhibition and differentiation effects.
- Similar outcomes were observed in primary myeloma cells.
Conclusions:
- Rosiglitazone (RGZ) effectively induces cell differentiation and inhibits proliferation in myeloma cells.
- Concomitant treatment with all-trans retinoic acid (ATRA) potentiates the anti-myeloma effects of RGZ.
