Establishment and characterization of bortezomib-resistant U266 cell line: Constitutive activation of NF-κB-mediated cell signals and/or alterations of ubiquitylation-related genes reduce bortezomib-induced apoptosis

Juwon Park, Eun Kyung Bae, Chansu Lee, Jee Hye Choi, Woo June Jung, Kwang Sung Ahn, Sung Soo Yoon

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Bortezomib has been known as the most promising anti-cancer drug for multiple myeloma (MM). However, recent studies reported that not all MM patients respond to bortezomib. To overcome such a stumbling-block, studies are needed to clarify the mechanisms of bortezomib resistance. In this study, we established a bortezomib-resistant cell line (U266/velR), and explored its biological characteristics. The U266/velR showed reduced sensitivity to bortezomib, and also showed crossresistance to the chemically unrelated drug thalidomide. U266/ velR cells had a higher proportion of CD138 negative subpopulation, known as stem-like feature, compared to parental U266 cells. U266/velR showed relatively less inhibitory effect of prosurvival NF-κB signaling by bortezomib. Further analysis of RNA microarray identified genes related to ubiquitination that were differentially regulated in U266/velR. Moreover, the expression level of CD52 in U266 cells was associated with bortezomib response. Our findings provide the basis for developing therapeutic strategies in bortezomib-resistant relapsed and refractory MM patients.

Original languageEnglish
Pages (from-to)274-279
Number of pages6
JournalBMB Reports
Volume47
Issue number5
DOIs
StatePublished - May 2014
Externally publishedYes

Keywords

  • Bortezomib resistance
  • Human multiple myeloma U266 cell line
  • NF-κB signaling
  • RNA microarray
  • Soft-agar forming assay

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