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Down-regulation of CD9 by methylation decreased bortezomib sensitivity in multiple myeloma.

Hu X, Xuan H, Du H, Jiang H, Huang J - PLoS ONE (2014)

Bottom Line: CD9 expression obviously increased bortezomib sensitivity through inducing apoptosis, significantly inhibiting U266 cells' adhesion to HS-5 and primary bone marrow stromal cells, but increasing U266 cells' adhesion to fibronectin.CD9 expression also significantly inhibited U266 cell migration.Combination therapy with de-methylation reagent 5-Aza-2-deoxycytidine may prove useful to the development of novel strategies for the treatment of bortezomib-resistant MM patients.

View Article: PubMed Central - PubMed

Affiliation: Biomedical Research Center, Sir Run Run Shaw Hospital, Zhejiang University and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.

ABSTRACT
Bortezomib therapy has been proven successful for the treatment of relapsed and/or refractory multiple myeloma (MM). However, both intrinsic and acquired resistance has already been observed. In this study, we explored the relationship between CD9 expression and bortezomib sensitivity in MM. We found that down-regulation of CD9 by methylation decreased bortezomib sensitivity in multiple myeloma. CD9 expression obviously increased bortezomib sensitivity through inducing apoptosis, significantly inhibiting U266 cells' adhesion to HS-5 and primary bone marrow stromal cells, but increasing U266 cells' adhesion to fibronectin. CD9 expression also significantly inhibited U266 cell migration. The mechanisms may include: the endoplasmic reticulum stress pathway, cell adhesion related signaling pathway and osteoclast differentiation related signaling pathway. Combination therapy with de-methylation reagent 5-Aza-2-deoxycytidine may prove useful to the development of novel strategies for the treatment of bortezomib-resistant MM patients.

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Related in: MedlinePlus

CD9 stablly transfected U266 cells construction and the effects of CD9 expression in U266 cell viability, apoptosis, adhesion and migration.(A) CD9 expression was confirmed by RT-PCR and western blot analysis. (B) CD9 expression obviously increased the bortezomib sensitivity compared to controls, *: p<0.05. (C) Bortezomib significantly promoted the apoptosis of U266/CD9 cells. *: p<0.05. (D) CD9 expression significantly inhibited U266 cells adhesion to bone marrow stromal cells HS-5. *: p<0.05. (E) CD9 expression significantly inhibited U266 cells' adhesion to the primary bone marrow stromal cells. *: p<0.05. (F) CD9 expression significantly increased U266 cells' adhesion to fibronectin. *: p<0.05. (G) CD9 expression significantly inhibited U266 cell migration. *: p<0.05.
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pone-0095765-g003: CD9 stablly transfected U266 cells construction and the effects of CD9 expression in U266 cell viability, apoptosis, adhesion and migration.(A) CD9 expression was confirmed by RT-PCR and western blot analysis. (B) CD9 expression obviously increased the bortezomib sensitivity compared to controls, *: p<0.05. (C) Bortezomib significantly promoted the apoptosis of U266/CD9 cells. *: p<0.05. (D) CD9 expression significantly inhibited U266 cells adhesion to bone marrow stromal cells HS-5. *: p<0.05. (E) CD9 expression significantly inhibited U266 cells' adhesion to the primary bone marrow stromal cells. *: p<0.05. (F) CD9 expression significantly increased U266 cells' adhesion to fibronectin. *: p<0.05. (G) CD9 expression significantly inhibited U266 cell migration. *: p<0.05.

Mentions: In order to study the expression of CD9 and its corresponding cell behavior changes in myeloma cells and their microenvironment, we transfected CD9 in U266 cells and selected the stably transfected cells by flow sorting. CD9 expression was confirmed by RT-PCR and western blot analysis (Figure 3A).


Down-regulation of CD9 by methylation decreased bortezomib sensitivity in multiple myeloma.

Hu X, Xuan H, Du H, Jiang H, Huang J - PLoS ONE (2014)

CD9 stablly transfected U266 cells construction and the effects of CD9 expression in U266 cell viability, apoptosis, adhesion and migration.(A) CD9 expression was confirmed by RT-PCR and western blot analysis. (B) CD9 expression obviously increased the bortezomib sensitivity compared to controls, *: p<0.05. (C) Bortezomib significantly promoted the apoptosis of U266/CD9 cells. *: p<0.05. (D) CD9 expression significantly inhibited U266 cells adhesion to bone marrow stromal cells HS-5. *: p<0.05. (E) CD9 expression significantly inhibited U266 cells' adhesion to the primary bone marrow stromal cells. *: p<0.05. (F) CD9 expression significantly increased U266 cells' adhesion to fibronectin. *: p<0.05. (G) CD9 expression significantly inhibited U266 cell migration. *: p<0.05.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4008425&req=5

pone-0095765-g003: CD9 stablly transfected U266 cells construction and the effects of CD9 expression in U266 cell viability, apoptosis, adhesion and migration.(A) CD9 expression was confirmed by RT-PCR and western blot analysis. (B) CD9 expression obviously increased the bortezomib sensitivity compared to controls, *: p<0.05. (C) Bortezomib significantly promoted the apoptosis of U266/CD9 cells. *: p<0.05. (D) CD9 expression significantly inhibited U266 cells adhesion to bone marrow stromal cells HS-5. *: p<0.05. (E) CD9 expression significantly inhibited U266 cells' adhesion to the primary bone marrow stromal cells. *: p<0.05. (F) CD9 expression significantly increased U266 cells' adhesion to fibronectin. *: p<0.05. (G) CD9 expression significantly inhibited U266 cell migration. *: p<0.05.
Mentions: In order to study the expression of CD9 and its corresponding cell behavior changes in myeloma cells and their microenvironment, we transfected CD9 in U266 cells and selected the stably transfected cells by flow sorting. CD9 expression was confirmed by RT-PCR and western blot analysis (Figure 3A).

Bottom Line: CD9 expression obviously increased bortezomib sensitivity through inducing apoptosis, significantly inhibiting U266 cells' adhesion to HS-5 and primary bone marrow stromal cells, but increasing U266 cells' adhesion to fibronectin.CD9 expression also significantly inhibited U266 cell migration.Combination therapy with de-methylation reagent 5-Aza-2-deoxycytidine may prove useful to the development of novel strategies for the treatment of bortezomib-resistant MM patients.

View Article: PubMed Central - PubMed

Affiliation: Biomedical Research Center, Sir Run Run Shaw Hospital, Zhejiang University and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.

ABSTRACT
Bortezomib therapy has been proven successful for the treatment of relapsed and/or refractory multiple myeloma (MM). However, both intrinsic and acquired resistance has already been observed. In this study, we explored the relationship between CD9 expression and bortezomib sensitivity in MM. We found that down-regulation of CD9 by methylation decreased bortezomib sensitivity in multiple myeloma. CD9 expression obviously increased bortezomib sensitivity through inducing apoptosis, significantly inhibiting U266 cells' adhesion to HS-5 and primary bone marrow stromal cells, but increasing U266 cells' adhesion to fibronectin. CD9 expression also significantly inhibited U266 cell migration. The mechanisms may include: the endoplasmic reticulum stress pathway, cell adhesion related signaling pathway and osteoclast differentiation related signaling pathway. Combination therapy with de-methylation reagent 5-Aza-2-deoxycytidine may prove useful to the development of novel strategies for the treatment of bortezomib-resistant MM patients.

Show MeSH
Related in: MedlinePlus