Page 119 - Haematologica May 2022

CDK12-transcription reprogramming in MCL and DLBCL
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Figure 6. Activation of MEK-ERK and PI3K-AKT-mTOR pathways contributes to MDR1 upregulation in THZ531-resistant cells. (A) Image-based cell-viability assays of primary MCL samples, cells (3x106) cells were seeded in a 384-well plate with extracellular matrix and lymphoma stromal cells. THZ531 and GSK343 at five serial diluted concentrations were added to the medium, and the plate was continuously imaged every 30 min for 144 h. All images were analyzed using a digital imaging analysis algorithm to detect cell viability based on membrane motion, and changes in viability were quantified by area under the curve (AUC). (B) Western blot of MDR1 and cleaved PARP protein expression in REC-1 cells after 24 h or 48 h of treatment with dimethylsulfoxide or indicated doses of THZ531 and/or AZD8055, BEZ235, or trametinib. (C) Dose-response curves of the REC-1 cells after treatment for 72 h with different doses of THZ531 and/or AZD8055, BEZ235 and trame- tinib. Data are shown as mean ± standard deviation of three technical replicates for each cell line. Data shown in (C) are representative of at least three independent experiments.
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