Skip to main content
Fig. 9 | Journal of Experimental & Clinical Cancer Research

Fig. 9

From: SF3B1 inhibition disrupts malignancy and prolongs survival in glioblastoma patients through BCL2L1 splicing and mTOR/ß-catenin pathways imbalances

Fig. 9

Pharmacological blockade of SF3B1 reveals AKT-mTOR and ß-catenin signaling pathways and BCL2L1 alternative splicing as major drivers of the pladienolide B antitumor effects in GBM. Heatmaps showing the western blot densitometric level (log2) of phosphorylated-proteins (a) and total-proteins levels (b) of several components of AKT/mTOR and ß-catenin pathways in GBM cells (U-87 MG and U-118 MG) after pladienolide B administration. c Images of western blot results showed in the previous heatmaps (a) and (b). d AKT-MTOR and ß-catenin pathways diagram showing the downregulated (in red) and upregulated (in the yellow box) components/processes after pladienolide B administration identified in this work. Expression levels of CCND1 (e) and MYC (f) as endpoints of AKT/mTOR and ß-catenin pathways in GBM cells (U-87 MG and U-118 MG), primary patient-derived GBM cells and in the preclinical-xenograft GBM model after pladienolide B administration. g BCL2L1 splicing variants produced by an alternative 5′ spliced site (A5SS) splicing event and associated with apoptosis and cell death pathway. h BCL2L1-xS/BCL2L1-xL ratio determined by qPCR in GBM cell lines (U-87 MG and U-118 MG), in the preclinical-xenograft GBM model, and in primary patient-derived GBM cells in response to pladienolide B treatment. i BCL2L1-xS/BCL2L1-xL ratio determined by qPCR in primary non-tumor brain cell culture after pladienolide B administration. PSI of BCL2L1 A5SS event in GBM cell lines (U-87 MG and U-118 MG) (j), in primary patient-derived GBM cells (k), and the preclinical-xenograft GBM model (l) in response to pladienolide B treatment. m Validation of designed antisense oligonucleotides (ASOs; ASO1_BCL2L1 and ASO3_BCL2L1) by determination of PSI of BCL2L1 A5SS event in GBM cell lines (U-87 MG and U-118 MG; n = 3). n Proliferation rate in GBM cells in response to control, pladienolide B, ASO1_BCL2L + pladienolide B, and ASO3_BCL2L1 + pladienolide B cells (n = 3). The % has been calculated with the control, ASO1_BCL2L1 and ASO3_BCL2L1 transfected cells (without pladienolide B treatment) of each condition. Asterisks and symbols (*P < 0.05; **P < 0.01; ***/###/††† P < 0.001) indicate statistically significant differences across different conditions (i.e.; pladienolide B vs. control; ASO1_BCL2L1+ pladienolide B vs. pladienolide B; ASO2_BCL2L1+ pladienolide B vs. pladienolide B, respectively). Plus symbol (+) indicates a tendency between conditions (+P > 0.05 < 0.1)

Back to article page