Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Nov;23(11):2181-3.
doi: 10.1038/leu.2009.123. Epub 2009 Jun 11.

Acquisition of a multidrug-resistant phenotype with a proteasome inhibitor in multiple myeloma

Acquisition of a multidrug-resistant phenotype with a proteasome inhibitor in multiple myeloma

D Gutman et al. Leukemia. 2009 Nov.
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1. Cell viability of KMS11 and KMS11R treated with epoxomicin and bortezomib
Cells were treated with the indicated concentrations of epoxomicin (A) or bortezomib (B) for 24 h. Cell viability was determined by flow cytometry after annexin-V- FITC/ PI staining. The data are presented as the mean (± SD) of three independent experiments. *p<0.05, **p<0.01, ***P<0.001
Figure 2
Figure 2. Expression and activity of the MDR protein P Glycoprotein
(A) Western Blot analysis of untreated KMS11 and KMS11R cells as well as cells treated with the indiated concentrations of epoxomicin for 24 h. A murine liver extract (MLE2) was used as a positive control for P-gP expression. (B) KMS11 (black histograms) and KMS11R (grey histograms) cells were treated with the indicated concentrations of doxorubicin for 24 h and the drug uptake was measured by flow cytometry. The data are representative at least three independent experiments.
Figure 3
Figure 3. Verapamil treatment of KMS11R restores sensitivity to epoxomicin
(A). KMS11 (black histograms) and KMS11R (grey histograms) cells were treated with 20 nM epoxomicin as a single agent or in combination with 40 μM verapamil. Cell viability was determined by flow cytometry after annexin-V- FITC/PI staining. Similar results were found using a range of expoximicin concentrations from 5 nM to 20 nM (not shown). The data are presented as the mean (± SD) of three independent experiments. **p <0.01. (B). KMS11 and KMS11R cells were treated with 0.25 μM doxorubicin in the presence (lower panel) or absence (upper panel) of 40 μM verapamil for 24 h and drug uptake measured by flow cytometry.

References

    1. Kyle RA, Vincent Rajkumar S. Treatment of multiple myeloma: an emphasis on new developments. Ann Med. 2006;38:111–115. - PubMed
    1. McConkey DJ, Zhu K. Mechanisms of proteasome inhibitor action and resistance in cancer. Drug Resist Updat. 2008;11:164–179. - PubMed
    1. Almond JB, Cohen GM. The proteasome: a novel target for cancer chemotherapy. Leukemia. 2002;16:433–443. - PubMed
    1. Demo SD, Kirk CJ, Aujay MA, Buchholz TJ, Dajee M, Ho MN, et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res. 2007;67:6383–6391. - PubMed
    1. Obeng EA, Carlson LM, Gutman DM, Harrington WJ, Jr., Lee KP, Boise LH. Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood. 2006;107:4907–4916. - PMC - PubMed

Publication types