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KMID : 0624620140470050274
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BMB Reports
2014 Volume.47 No. 5 p.274 ~ p.279
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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
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Park Ju-Won
Bae Eun-Kyung
Lee Chan-Su
Choi Jee-Hye
Jung Woo-June
Ahn Kwang-Sung
Yoon Sung-Soo
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Abstract
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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.
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KEYWORD
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Bortezomib resistance, Human multiple myeloma U266 cell line, NF-κB signaling, RNA microarray, Soft-agar forming assay
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