Fig. 2: BCL-xL and MCL-1 antagonism enhance priming with PI3K/AKT/mTOR pathway inhibitors in MPM. | Nature Communications

Fig. 2: BCL-xL and MCL-1 antagonism enhance priming with PI3K/AKT/mTOR pathway inhibitors in MPM.

From: Dynamic BH3 profiling identifies pro-apoptotic drug combinations for the treatment of malignant pleural mesothelioma

Fig. 2

a Primary epithelioid MPM cells were treated as previously described in Fig. 1, in technical duplicate. Representative immunofluorescence microscopy images from MPM patient sample A (MPS:A). Images taken at tenfold magnification. Hoechst 33342 used to stain DNA (blue) and identify the number of cells/well. Pan-cytokeratin-488 antibody (green) used to identify epithelioid cells (parent population). From the parent population, cytochrome c positive cells % was determined using cytochrome c-647 antibody (red). DMSO treatment is a negative control for cytochrome c loss. Non-hit is a drug treatment that didn’t score above the hit threshold (no drug-induced priming). Top hit is the drug treatment that scored the highest mean Z-score (highest drug-induced priming) for this patient sample, first red dot in Fig. 1b. Scale bar is 100 µm. b Schematic showing drug targets for BH3 mimetics, BH3 peptides and PI3K/AKT/mTOR pathway inhibitors used in this paper. All drugs (not BH3 peptides) shown here are included in CROCS list except A-1331852 (because it’s not in clinical trials yet). BH3 peptides are peptides derived from the BH3 ___domain of the pro-apoptotic BH3-only Bcl-2 family members and are used in BH3 profiling/DBP assay. c Graph showing mean Z-score for top ten most common hits and hits with highest mean across n = 13 MPM patient samples. d Graph showing mean Z-score for navitoclax, S63845 or venetoclax in combination with PI3K/AKT/mTOR pathway inhibitors (combinations and single agents), across n = 13 MPM patient samples.

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