Abstract | OBJECTIVE: METHODS: The mRNA expression of RelB in CD5⁺ CD19⁺ CLL cells from BM was analyzed by reverse transcription PCR (RT-PCR). The RelB activity was examined by electromobility shift assay (EMSA) and an ELISA-based NF-κB family transcription factor activity assay. CLL cells were classified into RelB+ and RelB- groups according to RelB activity. The frequencies of cell death of CLL cells cultured with human bone marrow stromal cells (hBMSCs) after treatment with PS-341, MG-132 or fludarabine were determined by PI staining. RESULTS: RelB mRNA expression and RelB activity could be detected in CLL cells at variable levels. Fludarabine (10 μmol/L), MG-132 (1 μmol/L) and PS-341 (1 μmol/L) could induce cell death of RelB+ and RelB- CLL cells co-cultured with hBMSCs in a time dependent manner. There was no significant difference in the fludarabine sensitivity between RelB+ and RelB- CLL cells, and the frequencies of cell death of RelB+ and RelB- CLL cells were (61.11 ± 6.91)% and (67.57 ± 9.45)%, respectively, when treated with fludarabine for 72 h. RelB+ CLL cells were more sensitive to MG-132 than RelB- CLL cells for 72 h, and the frequencies of cell death were (66.22 ± 3.39)% and (51.07 ± 5.93)%, respectively. RelB+ CLL cells were more sensitive to PS-341 than RelB- CLL cells for 24 and 48 h treatment, and the frequencies of cell death of RelB+ and RelB- CLL cells were (75.50 ± 4.66)% and (66.32 ± 10.20)% for 24 h, (92.11 ± 3.14)% and (85.84 ± 5.81)% for 48 h treatment, respectively. CONCLUSION: The alternative NF-κB activity was detected in bone marrow derived CLL cells. Enhancement of RelB activity may increase CLL cells' sensitivity to proteasome inhibitor bortezomib and MG-132. However, the sensitivity of CLL cells to fludarabine had no relationship to RelB activity.
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Authors | Jingjing Xu, Peng Zhou, Aining Sun, Feng Guo |
Journal | Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi
(Zhonghua Xue Ye Xue Za Zhi)
Vol. 35
Issue 6
Pg. 524-7
(Jun 2014)
ISSN: 0253-2727 [Print] China |
PMID | 24985177
(Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- NF-kappa B
- Proteasome Inhibitors
- RELB protein, human
- RNA, Messenger
- Transcription Factor RelB
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Topics |
- Cell Death
(drug effects)
- Drug Resistance, Neoplasm
- Humans
- Leukemia, Lymphocytic, Chronic, B-Cell
(metabolism, pathology)
- NF-kappa B
(metabolism)
- Proteasome Inhibitors
(pharmacology)
- RNA, Messenger
(genetics)
- Transcription Factor RelB
(genetics, metabolism)
- Tumor Cells, Cultured
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