Skip to main content
. 2020 Feb 12;12(2):429. doi: 10.3390/cancers12020429

Figure 4.

Figure 4

Mitoxantrone-resistant NCI-H460 cells with basal upregulation of ABCG2 are cross-resistant to MLN4924. (A) ABCG2 protein expression is upregulated in NCI-H460/MX20 cells compared to NCI-H460 parentals. ABCG2 expression was determined in parental and NCI-H460/MX20 cells by immunoblotting. (B) NCI-H460/MX20 cells are resistant to MLN4924 treatment. Parental and resistant cells were treated with the indicated concentrations of MLN4924 for 72 h. Cell viability was measured by MTT assay. Mean ± SD, n = 3. (C) MLN4924 displays reduced potency in target inhibition and stabilization of downstream NEDD8 substrates, including NRF2, p21, and p27, in NCI-H460/MX20 cells. Cells were treated with the indicated concentrations of MLN4924 for 24 h. Protein expression levels were determined by immunoblotting. (D) The ABCG2 inhibitor YHO-13351 overcomes the effects of ABCG2 overexpression. NCI-H460 and NCI-H460/MX20 cells were treated with the indicated concentrations of MLN4924 with or without 2 μM YHO-13351 for 24 h. Protein expression levels were determined by immunoblotting. (E) ABCG2 inhibitors YHO-13351 and fumitremorgin C (FTC) enhance the cytotoxic activity of MLN4924 in NCI-H460/MX20 cells. Cells were treated with the indicated concentrations of MLN4924 and 2 μM YHO-13351 or 5 μM FTC for 72 h. Cell viability was determined by MTT assay. Mean ± SD, n = 3.