1. Reversal of Bortezomib Resistance in Myelodysplastic Syndrome Cells by MAPK Inhibitors.
- Author
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Yue, Yingxing, Wang, Ying, He, Yang, Yang, Shuting, Chen, Zixing, Wang, Yuanyuan, Xing, Shanshan, Shen, Congcong, Amin, Hesham M., Wu, Depei, and Song, Yao-Hua
- Subjects
BORTEZOMIB ,MYELODYSPLASTIC syndromes ,MITOGEN-activated protein kinases ,MULTIPLE myeloma ,CELL cycle ,APOPTOSIS ,AUTOPHAGY - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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