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Fig. 3 | BMC Cancer

Fig. 3

From: Upregulation of FOXM1 leads to diminished drug sensitivity in myeloma

Fig. 3

Upregulation of FOXM1 promotes drug resistance of myeloma in vitro. a Bar diagram depicting the half maximal inhibitory concentrations (IC50) of bortezomib (Bz) and doxorubicine (Dox) in XG1 and CAG myeloma cells expressing elevated (FOXM1Hi) or normal (FOXM1N) levels of the transcription factor. Cells were grown for 1 week in bulk suspension culture in presence of a log2 dose range of either drug. IC50 was determined using non-linear regression analysis of dose response curves (GraphPad Prism 7 software). Hi-to-N ratios of IC50 (indicated by vertical short lines and numbers) reflect the magnitude by which overexpression of FOXM1 reduced drug-induced cell killing. b Representative flow histograms comparing levels of drug-induced apoptosis in paired FOXM1Hi/FOXM1N samples of XG1 (upper half) and CAG (lower half) cells treated with 6 nM Bz (center column) or 0.1 μM Dox (right column). Cells left untreated were used as control (left column). APC (allophycocyanin)-conjugated antibody to annexin V was used to determine the fraction of cells undergoing apoptosis (indicated as percentages above black horizontal lines). In all cases, death was attenuated by enforced expression of FOXM1. c Photographic images of soft-agar plates containing colonies of FOXM1Hi and FOXM1N CAG myeloma cells. Cells were treated with the indicated dose of bortezomib or left untreated. Clonogenic growth expressed as percentage of cells able to form colonies is given in the insets. d Bar diagram depicting soft-agar clonogenicity of FOXM1Hi/FOXM1N CAG or XG1 cells treated with 2 nM Bz or 0.1 μM Dox. Cells left untreated were used as control (Co). The Hi-to-N ratios of the average colony numbers, determined in triplicate experiments, are indicated by vertical numbers next to vertical lines. The ratios reflect the extent by which overexpression of FOXM1 mitigated drug-dependent inhibition of clonogenic growth

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