Reversal of bortezomib resistance in myelodysplastic syndrome cells by MAPK inhibitors.
The myelodysplastic syndromes (MDS) comprise a heterogeneous group of malignant neoplasms with distinctive clinicopathological features. Currently, there is no specific approach for the treatment of MDS. Here, we report that bortezomib (BTZ), a proteasome inhibitor that has been used to treat plasma...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3946707?pdf=render |
| _version_ | 1818022844184920064 |
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| author | Yingxing Yue Ying Wang Yang He Shuting Yang Zixing Chen Yuanyuan Wang Shanshan Xing Congcong Shen Hesham M Amin Depei Wu Yao-Hua Song |
| author_facet | Yingxing Yue Ying Wang Yang He Shuting Yang Zixing Chen Yuanyuan Wang Shanshan Xing Congcong Shen Hesham M Amin Depei Wu Yao-Hua Song |
| author_sort | Yingxing Yue |
| collection | DOAJ |
| description | The myelodysplastic syndromes (MDS) comprise a heterogeneous group of malignant neoplasms with distinctive clinicopathological features. Currently, there is no specific approach for the treatment of MDS. Here, we report that bortezomib (BTZ), a proteasome inhibitor that has been used to treat plasma cell myeloma, induced G2/M phase cycle arrest in the MDS cell line SKM-1 through upregulation of Wee1, a negative regulator of G2/M phase transition. Treatment by BTZ led to reduced SKM-1 cell viability as well as increased apoptosis and autophagy. The BTZ-induced cell death was associated with reduced expression of p-ERK. To elucidate the implications of downregulation of p-ERK, we established the BTZ resistant cell line SKM-1R. Our data show that resistance to BTZ-induced apoptosis could be reversed by the MEK inhibitors U0126 or PD98059. Our results suggest that MAPK pathway may play an important role in mediating BTZ resistance. |
| first_indexed | 2024-12-10T03:34:53Z |
| format | Article |
| id | doaj.art-5e3dd4abd63c48e9a877e1dcc08f9109 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T03:34:53Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5e3dd4abd63c48e9a877e1dcc08f91092022-12-22T02:03:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9099210.1371/journal.pone.0090992Reversal of bortezomib resistance in myelodysplastic syndrome cells by MAPK inhibitors.Yingxing YueYing WangYang HeShuting YangZixing ChenYuanyuan WangShanshan XingCongcong ShenHesham M AminDepei WuYao-Hua SongThe myelodysplastic syndromes (MDS) comprise a heterogeneous group of malignant neoplasms with distinctive clinicopathological features. Currently, there is no specific approach for the treatment of MDS. Here, we report that bortezomib (BTZ), a proteasome inhibitor that has been used to treat plasma cell myeloma, induced G2/M phase cycle arrest in the MDS cell line SKM-1 through upregulation of Wee1, a negative regulator of G2/M phase transition. Treatment by BTZ led to reduced SKM-1 cell viability as well as increased apoptosis and autophagy. The BTZ-induced cell death was associated with reduced expression of p-ERK. To elucidate the implications of downregulation of p-ERK, we established the BTZ resistant cell line SKM-1R. Our data show that resistance to BTZ-induced apoptosis could be reversed by the MEK inhibitors U0126 or PD98059. Our results suggest that MAPK pathway may play an important role in mediating BTZ resistance.http://europepmc.org/articles/PMC3946707?pdf=render |
| spellingShingle | Yingxing Yue Ying Wang Yang He Shuting Yang Zixing Chen Yuanyuan Wang Shanshan Xing Congcong Shen Hesham M Amin Depei Wu Yao-Hua Song Reversal of bortezomib resistance in myelodysplastic syndrome cells by MAPK inhibitors. PLoS ONE |
| title | Reversal of bortezomib resistance in myelodysplastic syndrome cells by MAPK inhibitors. |
| title_full | Reversal of bortezomib resistance in myelodysplastic syndrome cells by MAPK inhibitors. |
| title_fullStr | Reversal of bortezomib resistance in myelodysplastic syndrome cells by MAPK inhibitors. |
| title_full_unstemmed | Reversal of bortezomib resistance in myelodysplastic syndrome cells by MAPK inhibitors. |
| title_short | Reversal of bortezomib resistance in myelodysplastic syndrome cells by MAPK inhibitors. |
| title_sort | reversal of bortezomib resistance in myelodysplastic syndrome cells by mapk inhibitors |
| url | http://europepmc.org/articles/PMC3946707?pdf=render |
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