Article

Triptolide enhances the sensitivity of multiple myeloma cells to dexamethasone via microRNAs.

Department of Hematology, Zhejiang University School of Medicine, Zhejiang Province, People's Republic of China.
Leukemia & lymphoma (impact factor: 2.4). 02/2012; 53(6):1188-95. DOI:10.3109/10428194.2011.638069 pp.1188-95
Source: PubMed

ABSTRACT Recently triptolide (TPL) has been proved to have the capacity to inhibit the proliferation of multiple myeloma (MM) cells as well as leukemic cells in vitro. In the present study, we found a synergistic effect when TPL was added to dexamethasone to induce apoptosis in MM.1S cells. This combination induced a significantly higher proportion of apoptotic cells compared with those treated with each drug separately. TPL down-regulated the expression of miR142 - 5p and miR181a, which have been shown to inhibit glucocorticoid receptor (GR) expression. MicroRNA mimics and inhibitors inhibited or enhanced the synergistic effect between TPL and dexamethasone in inducing apoptosis in MM.1S cells, suggesting an important role of miR142 - 5p and miR181a in GR regulation by TPL. The in vitro proapoptotic effect of TPL associated with dexamethasone reveals a new lead for further clinical investigation into the treatment of patients with MM with TPL.

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Keywords

clinical investigation
 
combination induced
 
dexamethasone
 
glucocorticoid receptor
 
GR
 
GR regulation
 
higher proportion
 
induce apoptosis
 
leukemic cells
 
multiple myeloma
 
new lead
 
patients
 
synergistic effect
 
TPL
 
triptolide
 
vitro
 
vitro proapoptotic effect