Modulating metadherin expression levels affects pemetrexed sensitivity in MPM cell lines.
(A) Cell viability was assessed at varying concentrations of pemetrexed to calculate IC50 values. MTDH overexpression (red) rendered MPM cells less sensitive to treatment, requiring 2.2-fold (H2452), 1.3-fold (MSTO-211H), and 2.2-fold (H2373) higher doses of drug to reach IC50 levels. (B) Annexin V flow cytometry measured levels of apoptosis when H2373 cells were treated with a fixed dose (IC50) of pemetrexed. Cells overexpressing MTDH (MTDH-OE) had lower levels of apoptosis. (C) Cell viability was assessed at varying concentrations of pemetrexed to calculate IC50 values. MTDH knockdown (red) rendered MPM cells more sensitive to treatment with pemetrexed, requiring 5.8-fold (H2452), 2-fold (MSTO-211H), and 1.9-fold (H2373) lower doses of drug to reach IC50 levels. (D) Annexin V flow cytometry measured levels of apoptosis when H2373 cells were treated with a fixed dose (IC50) of pemetrexed. Cells with reduced expression of MTDH (MTDH-KD) had lower levels of apoptosis. Where applicable, data are presented as mean ± SE. Ctrl is a negative control. OE indicates gene overexpression. KD indicates gene suppression. * P < .05.